| anno_start anno_end anno_text entity_type sentence section | |
| 0 9 Structure evidence Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex TITLE | |
| 56 72 topoisomerase IV complex_assembly Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex TITLE | |
| 78 99 Klebsiella pneumoniae species Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex TITLE | |
| 130 154 Streptococcus pneumoniae species Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex TITLE | |
| 0 18 Crystal structures evidence Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 48 64 topoisomerase IV complex_assembly Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 70 83 Gram-negative taxonomy_domain Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 85 98 K. pneumoniae species Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 104 117 Gram-positive taxonomy_domain Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 119 132 S. pneumoniae species Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 134 143 bacterial taxonomy_domain Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 212 224 levofloxacin chemical Crystal structures of the cleavage complexes of topoisomerase IV from Gram-negative (K. pneumoniae) and Gram-positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. ABSTRACT | |
| 4 17 K. pneumoniae species For K. pneumoniae, this is the first high-resolution cleavage complex structure to be reported. ABSTRACT | |
| 70 79 structure evidence For K. pneumoniae, this is the first high-resolution cleavage complex structure to be reported. ABSTRACT | |
| 1 22 Klebsiella pneumoniae species Klebsiella pneumoniae is a Gram-negative bacterium that is responsible for a range of common infections, including pulmonary pneumonia, bloodstream infections and meningitis. ABSTRACT | |
| 28 51 Gram-negative bacterium taxonomy_domain Klebsiella pneumoniae is a Gram-negative bacterium that is responsible for a range of common infections, including pulmonary pneumonia, bloodstream infections and meningitis. ABSTRACT | |
| 19 29 Klebsiella taxonomy_domain Certain strains of Klebsiella have become highly resistant to antibiotics. ABSTRACT | |
| 65 73 bacteria taxonomy_domain Despite the vast amount of research carried out on this class of bacteria, the molecular structure of its topoisomerase IV, a type II topoisomerase essential for catalysing chromosomal segregation, had remained unknown. ABSTRACT | |
| 89 98 structure evidence Despite the vast amount of research carried out on this class of bacteria, the molecular structure of its topoisomerase IV, a type II topoisomerase essential for catalysing chromosomal segregation, had remained unknown. ABSTRACT | |
| 106 122 topoisomerase IV complex_assembly Despite the vast amount of research carried out on this class of bacteria, the molecular structure of its topoisomerase IV, a type II topoisomerase essential for catalysing chromosomal segregation, had remained unknown. ABSTRACT | |
| 126 147 type II topoisomerase protein_type Despite the vast amount of research carried out on this class of bacteria, the molecular structure of its topoisomerase IV, a type II topoisomerase essential for catalysing chromosomal segregation, had remained unknown. ABSTRACT | |
| 19 28 structure evidence In this paper, the structure of its DNA-cleavage complex is reported at 3.35 Å resolution. ABSTRACT | |
| 36 39 DNA chemical In this paper, the structure of its DNA-cleavage complex is reported at 3.35 Å resolution. ABSTRACT | |
| 28 32 ParC protein The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 33 49 breakage-reunion structure_element The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 54 58 ParE protein The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 59 65 TOPRIM structure_element The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 77 90 K. pneumoniae species The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 91 107 topoisomerase IV complex_assembly The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 113 116 DNA chemical The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 131 143 levofloxacin chemical The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 162 177 fluoroquinolone chemical The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. ABSTRACT | |
| 53 77 Streptococcus pneumoniae species This complex is compared with a similar complex from Streptococcus pneumoniae, which has recently been solved. ABSTRACT | |
| 1 11 Klebsiella taxonomy_domain Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 40 58 Enterobacteriaceae taxonomy_domain Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 69 90 Gram-negative bacilli taxonomy_domain Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 162 165 DNA chemical Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 176 189 K. pneumoniae species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 191 201 K. ozaenae species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 203 222 K. rhinoscleromatis species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 224 234 K. oxytoca species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 236 249 K. planticola species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 251 263 K. terrigena species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 268 286 K. ornithinolytica species Klebsiella is a genus belonging to the Enterobacteriaceae family of Gram-negative bacilli, which is divided into seven species with demonstrated similarities in DNA homology: K. pneumoniae, K. ozaenae, K. rhinoscleromatis, K. oxytoca, K. planticola, K. terrigena and K. ornithinolytica. INTRO | |
| 0 13 K. pneumoniae species K. pneumoniae is the most medically important species of the genus owing to its high resistance to antibiotics. INTRO | |
| 106 119 K. pneumoniae species Significant morbidity and mortality has been associated with an emerging, highly drug-resistant strain of K. pneumoniae characterized as producing the carbapenemase enzyme (KPC-producing bacteria; Nordmann et al., 2009). INTRO | |
| 151 164 carbapenemase protein_type Significant morbidity and mortality has been associated with an emerging, highly drug-resistant strain of K. pneumoniae characterized as producing the carbapenemase enzyme (KPC-producing bacteria; Nordmann et al., 2009). INTRO | |
| 187 195 bacteria taxonomy_domain Significant morbidity and mortality has been associated with an emerging, highly drug-resistant strain of K. pneumoniae characterized as producing the carbapenemase enzyme (KPC-producing bacteria; Nordmann et al., 2009). INTRO | |
| 37 68 in vitro susceptibility testing experimental_method However, common treatments (based on in vitro susceptibility testing) are the polymyxins, tigecycline and, less frequently, aminoglycoside antibiotics (Arnold et al., 2011). INTRO | |
| 78 88 polymyxins chemical However, common treatments (based on in vitro susceptibility testing) are the polymyxins, tigecycline and, less frequently, aminoglycoside antibiotics (Arnold et al., 2011). INTRO | |
| 90 101 tigecycline chemical However, common treatments (based on in vitro susceptibility testing) are the polymyxins, tigecycline and, less frequently, aminoglycoside antibiotics (Arnold et al., 2011). INTRO | |
| 124 138 aminoglycoside chemical However, common treatments (based on in vitro susceptibility testing) are the polymyxins, tigecycline and, less frequently, aminoglycoside antibiotics (Arnold et al., 2011). INTRO | |
| 92 108 fluoroquinolones chemical Another effective strategy involves the limited use of certain antimicrobials, specifically fluoroquinolones and cephalosporins (Gasink et al., 2009). INTRO | |
| 113 128 cephalosporins chemical Another effective strategy involves the limited use of certain antimicrobials, specifically fluoroquinolones and cephalosporins (Gasink et al., 2009). INTRO | |
| 69 80 β-lactamase protein_type These include combinations of existing β-lactam antibiotics with new β-lactamase inhibitors able to circumvent KPC resistance. INTRO | |
| 0 13 Neoglycosides chemical Neoglycosides are novel aminoglycosides that have activity against KPC-producing bacteria that are also being developed (Chen et al., 2012). INTRO | |
| 24 39 aminoglycosides chemical Neoglycosides are novel aminoglycosides that have activity against KPC-producing bacteria that are also being developed (Chen et al., 2012). INTRO | |
| 81 89 bacteria taxonomy_domain Neoglycosides are novel aminoglycosides that have activity against KPC-producing bacteria that are also being developed (Chen et al., 2012). INTRO | |
| 0 29 Type II topoisomerase enzymes protein_type Type II topoisomerase enzymes play important roles in prokaryotic and eukaryotic DNA replication, recombination and transcription (Drlica et al., 2008; Laponogov et al., 2013; Lee et al., 2013; Nitiss, 2009a ,b ; Schoeffler & Berger, 2008; Sissi & Palumbo, 2009; Vos et al., 2011; Wendorff et al., 2012; Wu et al., 2011, 2013). INTRO | |
| 54 65 prokaryotic taxonomy_domain Type II topoisomerase enzymes play important roles in prokaryotic and eukaryotic DNA replication, recombination and transcription (Drlica et al., 2008; Laponogov et al., 2013; Lee et al., 2013; Nitiss, 2009a ,b ; Schoeffler & Berger, 2008; Sissi & Palumbo, 2009; Vos et al., 2011; Wendorff et al., 2012; Wu et al., 2011, 2013). INTRO | |
| 70 80 eukaryotic taxonomy_domain Type II topoisomerase enzymes play important roles in prokaryotic and eukaryotic DNA replication, recombination and transcription (Drlica et al., 2008; Laponogov et al., 2013; Lee et al., 2013; Nitiss, 2009a ,b ; Schoeffler & Berger, 2008; Sissi & Palumbo, 2009; Vos et al., 2011; Wendorff et al., 2012; Wu et al., 2011, 2013). INTRO | |
| 81 84 DNA chemical Type II topoisomerase enzymes play important roles in prokaryotic and eukaryotic DNA replication, recombination and transcription (Drlica et al., 2008; Laponogov et al., 2013; Lee et al., 2013; Nitiss, 2009a ,b ; Schoeffler & Berger, 2008; Sissi & Palumbo, 2009; Vos et al., 2011; Wendorff et al., 2012; Wu et al., 2011, 2013). INTRO | |
| 3 11 bacteria taxonomy_domain In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 13 29 topoisomerase IV complex_assembly In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 33 41 tetramer oligomeric_state In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 49 53 ParC protein In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 62 66 ParE protein In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 157 163 gyrase protein_type In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 167 177 GyrA2GyrB2 complex_assembly In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 178 186 tetramer oligomeric_state In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 199 202 DNA chemical In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 220 223 DNA chemical In bacteria, topoisomerase IV, a tetramer of two ParC and two ParE subunits, unlinks daughter chromosomes prior to cell division, whereas the related enzyme gyrase, a GyrA2GyrB2 tetramer, supercoils DNA and helps unwind DNA at replication forks. INTRO | |
| 37 40 DNA chemical Both enzymes act via a double-strand DNA break involving a cleavage complex and are targets for quinolone antimicrobials that act by trapping these enzymes at the DNA-cleavage stage and preventing strand re-joining (Drlica et al., 2008). INTRO | |
| 163 166 DNA chemical Both enzymes act via a double-strand DNA break involving a cleavage complex and are targets for quinolone antimicrobials that act by trapping these enzymes at the DNA-cleavage stage and preventing strand re-joining (Drlica et al., 2008). INTRO | |
| 0 12 Levofloxacin chemical Levofloxacin is a broad-spectrum third-generation fluoroquinolone antibiotic. INTRO | |
| 21 34 Gram-positive taxonomy_domain It is active against Gram-positive and Gram-negative bacteria and functions by inhibiting gyrase and topoisomerase IV (Drlica & Zhao, 1997; Laponogov et al., 2010). INTRO | |
| 39 61 Gram-negative bacteria taxonomy_domain It is active against Gram-positive and Gram-negative bacteria and functions by inhibiting gyrase and topoisomerase IV (Drlica & Zhao, 1997; Laponogov et al., 2010). INTRO | |
| 90 96 gyrase protein_type It is active against Gram-positive and Gram-negative bacteria and functions by inhibiting gyrase and topoisomerase IV (Drlica & Zhao, 1997; Laponogov et al., 2010). INTRO | |
| 101 117 topoisomerase IV complex_assembly It is active against Gram-positive and Gram-negative bacteria and functions by inhibiting gyrase and topoisomerase IV (Drlica & Zhao, 1997; Laponogov et al., 2010). INTRO | |
| 82 98 fluoroquinolones chemical Acquiring a deep structural and functional understanding of the mode of action of fluoroquinolones (Tomašić & Mašič, 2014) and the development of new drugs targeted against topoisomerase IV and gyrase from a wide range of Gram-positive and Gram-negative pathogenic bacteria are highly active areas of current research directed at overcoming the vexed problem of drug resistance (Bax et al., 2010; Chan et al., 2015; Drlica et al., 2014; Mutsaev et al., 2014; Pommier, 2013; Srikannathasan et al., 2015). INTRO | |
| 173 189 topoisomerase IV complex_assembly Acquiring a deep structural and functional understanding of the mode of action of fluoroquinolones (Tomašić & Mašič, 2014) and the development of new drugs targeted against topoisomerase IV and gyrase from a wide range of Gram-positive and Gram-negative pathogenic bacteria are highly active areas of current research directed at overcoming the vexed problem of drug resistance (Bax et al., 2010; Chan et al., 2015; Drlica et al., 2014; Mutsaev et al., 2014; Pommier, 2013; Srikannathasan et al., 2015). INTRO | |
| 194 200 gyrase protein_type Acquiring a deep structural and functional understanding of the mode of action of fluoroquinolones (Tomašić & Mašič, 2014) and the development of new drugs targeted against topoisomerase IV and gyrase from a wide range of Gram-positive and Gram-negative pathogenic bacteria are highly active areas of current research directed at overcoming the vexed problem of drug resistance (Bax et al., 2010; Chan et al., 2015; Drlica et al., 2014; Mutsaev et al., 2014; Pommier, 2013; Srikannathasan et al., 2015). INTRO | |
| 222 235 Gram-positive taxonomy_domain Acquiring a deep structural and functional understanding of the mode of action of fluoroquinolones (Tomašić & Mašič, 2014) and the development of new drugs targeted against topoisomerase IV and gyrase from a wide range of Gram-positive and Gram-negative pathogenic bacteria are highly active areas of current research directed at overcoming the vexed problem of drug resistance (Bax et al., 2010; Chan et al., 2015; Drlica et al., 2014; Mutsaev et al., 2014; Pommier, 2013; Srikannathasan et al., 2015). INTRO | |
| 240 253 Gram-negative taxonomy_domain Acquiring a deep structural and functional understanding of the mode of action of fluoroquinolones (Tomašić & Mašič, 2014) and the development of new drugs targeted against topoisomerase IV and gyrase from a wide range of Gram-positive and Gram-negative pathogenic bacteria are highly active areas of current research directed at overcoming the vexed problem of drug resistance (Bax et al., 2010; Chan et al., 2015; Drlica et al., 2014; Mutsaev et al., 2014; Pommier, 2013; Srikannathasan et al., 2015). INTRO | |
| 265 273 bacteria taxonomy_domain Acquiring a deep structural and functional understanding of the mode of action of fluoroquinolones (Tomašić & Mašič, 2014) and the development of new drugs targeted against topoisomerase IV and gyrase from a wide range of Gram-positive and Gram-negative pathogenic bacteria are highly active areas of current research directed at overcoming the vexed problem of drug resistance (Bax et al., 2010; Chan et al., 2015; Drlica et al., 2014; Mutsaev et al., 2014; Pommier, 2013; Srikannathasan et al., 2015). INTRO | |
| 44 59 X-ray structure evidence Here, we report the first three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilized by levofloxacin. INTRO | |
| 65 78 K. pneumoniae species Here, we report the first three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilized by levofloxacin. INTRO | |
| 79 95 topoisomerase IV complex_assembly Here, we report the first three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilized by levofloxacin. INTRO | |
| 96 105 ParC/ParE complex_assembly Here, we report the first three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilized by levofloxacin. INTRO | |
| 128 131 DNA chemical Here, we report the first three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilized by levofloxacin. INTRO | |
| 146 158 levofloxacin chemical Here, we report the first three-dimensional X-ray structure of a K. pneumoniae topoisomerase IV ParC/ParE cleavage complex with DNA stabilized by levofloxacin. INTRO | |
| 4 21 crystal structure evidence The crystal structure provides structural information on topoisomerase IV from K. pneumoniae, a pathogen for which drug resistance is a serious concern. INTRO | |
| 57 73 topoisomerase IV complex_assembly The crystal structure provides structural information on topoisomerase IV from K. pneumoniae, a pathogen for which drug resistance is a serious concern. INTRO | |
| 79 92 K. pneumoniae species The crystal structure provides structural information on topoisomerase IV from K. pneumoniae, a pathogen for which drug resistance is a serious concern. INTRO | |
| 4 13 structure evidence The structure of the ParC/ParE–DNA–levofloxacin binding site highlights the details of the cleavage-complex assembly that are essential for the rational design of Klebsiella topoisomerase inhibitors. INTRO | |
| 21 30 ParC/ParE complex_assembly The structure of the ParC/ParE–DNA–levofloxacin binding site highlights the details of the cleavage-complex assembly that are essential for the rational design of Klebsiella topoisomerase inhibitors. INTRO | |
| 31 60 DNA–levofloxacin binding site site The structure of the ParC/ParE–DNA–levofloxacin binding site highlights the details of the cleavage-complex assembly that are essential for the rational design of Klebsiella topoisomerase inhibitors. INTRO | |
| 163 173 Klebsiella taxonomy_domain The structure of the ParC/ParE–DNA–levofloxacin binding site highlights the details of the cleavage-complex assembly that are essential for the rational design of Klebsiella topoisomerase inhibitors. INTRO | |
| 174 187 topoisomerase protein_type The structure of the ParC/ParE–DNA–levofloxacin binding site highlights the details of the cleavage-complex assembly that are essential for the rational design of Klebsiella topoisomerase inhibitors. INTRO | |
| 8 23 co-crystallized experimental_method We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 28 41 K. pneumoniae species We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 42 58 topoisomerase IV complex_assembly We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 59 68 ParC/ParE complex_assembly We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 69 85 breakage-reunion structure_element We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 94 100 ParC55 protein We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 111 116 1–490 residue_range We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 122 126 ParE protein We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 127 133 TOPRIM structure_element We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 142 148 ParE30 protein We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 159 166 390–631 residue_range We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 188 191 DNA chemical We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 204 210 E-site site We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 227 239 levofloxacin chemical We have co-crystallized the K. pneumoniae topoisomerase IV ParC/ParE breakage-reunion domain (ParC55; residues 1–490) and ParE TOPRIM domain (ParE30; residues 390–631) with a precut 34 bp DNA duplex (the E-site), stabilized by levofloxacin. RESULTS | |
| 4 27 X-ray crystal structure evidence The X-ray crystal structure of the complex was determined to 3.35 Å resolution, revealing a closed ParC55 dimer flanked by two ParE30 monomers (Figs. 1 ▸, 2 ▸ and 3 ▸). RESULTS | |
| 92 98 closed protein_state The X-ray crystal structure of the complex was determined to 3.35 Å resolution, revealing a closed ParC55 dimer flanked by two ParE30 monomers (Figs. 1 ▸, 2 ▸ and 3 ▸). RESULTS | |
| 99 105 ParC55 protein The X-ray crystal structure of the complex was determined to 3.35 Å resolution, revealing a closed ParC55 dimer flanked by two ParE30 monomers (Figs. 1 ▸, 2 ▸ and 3 ▸). RESULTS | |
| 106 111 dimer oligomeric_state The X-ray crystal structure of the complex was determined to 3.35 Å resolution, revealing a closed ParC55 dimer flanked by two ParE30 monomers (Figs. 1 ▸, 2 ▸ and 3 ▸). RESULTS | |
| 127 133 ParE30 protein The X-ray crystal structure of the complex was determined to 3.35 Å resolution, revealing a closed ParC55 dimer flanked by two ParE30 monomers (Figs. 1 ▸, 2 ▸ and 3 ▸). RESULTS | |
| 134 142 monomers oligomeric_state The X-ray crystal structure of the complex was determined to 3.35 Å resolution, revealing a closed ParC55 dimer flanked by two ParE30 monomers (Figs. 1 ▸, 2 ▸ and 3 ▸). RESULTS | |
| 70 83 S. pneumoniae species The overall architecture of this complex is similar to that found for S. pneumoniae topoisomerase–DNA–drug complexes (Laponogov et al., 2009, 2010). RESULTS | |
| 9 13 6–30 residue_range Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 32 39 α-helix structure_element Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 40 42 α1 structure_element Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 50 54 ParC protein Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 81 85 ParE protein Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 109 113 ParE protein Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 151 155 ParC protein Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 156 161 dimer oligomeric_state Residues 6–30 of the N-terminal α-helix α1 of the ParC subunit again embrace the ParE subunit, ‘hugging’ the ParE subunits close to either side of the ParC dimer (Laponogov et al., 2010). RESULTS | |
| 0 11 Deletion of experimental_method Deletion of this ‘arm’ α1 results in loss of DNA-cleavage activity (Laponogov et al., 2007) and is clearly very important in complex stability (Fig. 3 ▸). RESULTS | |
| 18 21 arm structure_element Deletion of this ‘arm’ α1 results in loss of DNA-cleavage activity (Laponogov et al., 2007) and is clearly very important in complex stability (Fig. 3 ▸). RESULTS | |
| 23 25 α1 structure_element Deletion of this ‘arm’ α1 results in loss of DNA-cleavage activity (Laponogov et al., 2007) and is clearly very important in complex stability (Fig. 3 ▸). RESULTS | |
| 37 66 loss of DNA-cleavage activity protein_state Deletion of this ‘arm’ α1 results in loss of DNA-cleavage activity (Laponogov et al., 2007) and is clearly very important in complex stability (Fig. 3 ▸). RESULTS | |
| 51 57 ParC55 protein This structural feature was absent in our original ParC55 structure (Laponogov et al., 2007; Sohi et al., 2008). RESULTS | |
| 58 67 structure evidence This structural feature was absent in our original ParC55 structure (Laponogov et al., 2007; Sohi et al., 2008). RESULTS | |
| 24 37 topoisomerase protein_type The upper region of the topoisomerase complex consists of the E-subunit TOPRIM metal-binding domain formed of four parallel β-sheets and the surrounding α-helices. RESULTS | |
| 62 71 E-subunit protein The upper region of the topoisomerase complex consists of the E-subunit TOPRIM metal-binding domain formed of four parallel β-sheets and the surrounding α-helices. RESULTS | |
| 72 99 TOPRIM metal-binding domain structure_element The upper region of the topoisomerase complex consists of the E-subunit TOPRIM metal-binding domain formed of four parallel β-sheets and the surrounding α-helices. RESULTS | |
| 115 132 parallel β-sheets structure_element The upper region of the topoisomerase complex consists of the E-subunit TOPRIM metal-binding domain formed of four parallel β-sheets and the surrounding α-helices. RESULTS | |
| 153 162 α-helices structure_element The upper region of the topoisomerase complex consists of the E-subunit TOPRIM metal-binding domain formed of four parallel β-sheets and the surrounding α-helices. RESULTS | |
| 4 13 C-subunit protein The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 27 30 WHD structure_element The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 32 51 winged-helix domain structure_element The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 55 73 CAP-like structure structure_element The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 106 111 tower structure_element The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 128 136 U groove structure_element The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 174 180 G-gate structure_element The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 181 184 DNA chemical The C-subunit provides the WHD (winged-helix domain; a CAP-like structure; McKay & Steitz, 1981) and the ‘tower’ which form the U groove-shaped protein region into which the G-gate DNA binds with an induced U-shaped bend. RESULTS | |
| 10 16 C-gate structure_element The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 84 98 long α-helices structure_element The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 124 137 short α-helix structure_element The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 158 182 DNA-accommodating cavity site The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 201 207 T-gate structure_element The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 208 211 DNA chemical The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 235 248 S. pneumoniae species The lower C-gate region (Fig. 3 ▸) consists of the same disposition of pairs of two long α-helices terminated by a spanning short α-helix forming a 30 Å wide DNA-accommodating cavity through which the T-gate DNA passes as found in the S. pneumoniae complex. RESULTS | |
| 56 74 topoisomerases IV complex_assembly Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 80 93 K. pneumoniae species Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 98 111 S. pneumoniae species Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 151 164 topoisomerase protein_type Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 260 269 structure evidence Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 277 289 full complex protein_state Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 295 305 holoenzyme protein_state Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 315 329 CTD β-pinwheel structure_element Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 347 360 ATPase domain structure_element Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 368 372 open protein_state Owing to the structural similarity, it appears that the topoisomerases IV from K. pneumoniae and S. pneumoniae are likely to follow a similar overall topoisomerase catalytic cycle as shown in Fig. 4 ▸; we have confirmation of one intermediate from our recent structure of the full complex (the holoenzyme less the CTD β-pinwheel domain) with the ATPase domain in the open conformation (Laponogov et al., 2013). RESULTS | |
| 4 10 G-gate structure_element The G-gate DNA for the S. pneumoniae complex consists of an 18-base-pair E-site sequence (our designation for a DNA site which we first found from DNA-mapping studies; Leo et al., 2005; Arnoldi et al., 2013; Fig. 1 ▸). RESULTS | |
| 11 14 DNA chemical The G-gate DNA for the S. pneumoniae complex consists of an 18-base-pair E-site sequence (our designation for a DNA site which we first found from DNA-mapping studies; Leo et al., 2005; Arnoldi et al., 2013; Fig. 1 ▸). RESULTS | |
| 23 36 S. pneumoniae species The G-gate DNA for the S. pneumoniae complex consists of an 18-base-pair E-site sequence (our designation for a DNA site which we first found from DNA-mapping studies; Leo et al., 2005; Arnoldi et al., 2013; Fig. 1 ▸). RESULTS | |
| 73 79 E-site site The G-gate DNA for the S. pneumoniae complex consists of an 18-base-pair E-site sequence (our designation for a DNA site which we first found from DNA-mapping studies; Leo et al., 2005; Arnoldi et al., 2013; Fig. 1 ▸). RESULTS | |
| 112 120 DNA site site The G-gate DNA for the S. pneumoniae complex consists of an 18-base-pair E-site sequence (our designation for a DNA site which we first found from DNA-mapping studies; Leo et al., 2005; Arnoldi et al., 2013; Fig. 1 ▸). RESULTS | |
| 147 166 DNA-mapping studies experimental_method The G-gate DNA for the S. pneumoniae complex consists of an 18-base-pair E-site sequence (our designation for a DNA site which we first found from DNA-mapping studies; Leo et al., 2005; Arnoldi et al., 2013; Fig. 1 ▸). RESULTS | |
| 4 16 crystallized experimental_method The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 56 69 topoisomerase protein_type The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 70 78 tetramer oligomeric_state The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 86 97 presence of protein_state The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 98 101 DNA chemical The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 106 118 levofloxacin chemical The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 123 136 crystallizing experimental_method The crystallized complex was formed by turning over the topoisomerase tetramer in the presence of DNA and levofloxacin and crystallizing the product. RESULTS | |
| 17 30 K. pneumoniae species In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 53 69 co-crystallizing experimental_method In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 74 87 topoisomerase protein_type In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 88 96 tetramer oligomeric_state In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 112 123 presence of protein_state In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 139 150 pre-cleaved protein_state In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 151 154 DNA chemical In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 162 173 presence of protein_state In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 174 186 levofloxacin chemical In contrast, the K. pneumoniae complex was formed by co-crystallizing the topoisomerase tetramer complex in the presence of a 34-base-pair pre-cleaved DNA in the presence of levofloxacin. RESULTS | |
| 18 21 DNA chemical In both cases the DNA is bent into a U-form and bound snugly against the protein of the G-gate. RESULTS | |
| 37 43 U-form protein_state In both cases the DNA is bent into a U-form and bound snugly against the protein of the G-gate. RESULTS | |
| 48 53 bound protein_state In both cases the DNA is bent into a U-form and bound snugly against the protein of the G-gate. RESULTS | |
| 88 94 G-gate structure_element In both cases the DNA is bent into a U-form and bound snugly against the protein of the G-gate. RESULTS | |
| 48 51 DNA chemical We have been able to unambiguously read off the DNA sequences in the electron-density maps. RESULTS | |
| 69 90 electron-density maps evidence We have been able to unambiguously read off the DNA sequences in the electron-density maps. RESULTS | |
| 73 77 ParE protein There is 41.6% sequence identity and 54.4% sequence homology between the ParE subunit of K. pneumoniae and that of S. pneumoniae. RESULTS | |
| 89 102 K. pneumoniae species There is 41.6% sequence identity and 54.4% sequence homology between the ParE subunit of K. pneumoniae and that of S. pneumoniae. RESULTS | |
| 115 128 S. pneumoniae species There is 41.6% sequence identity and 54.4% sequence homology between the ParE subunit of K. pneumoniae and that of S. pneumoniae. RESULTS | |
| 8 12 ParC protein For the ParC subunits, the figures are 40.8 identity and 55.6% homology between the two organisms. RESULTS | |
| 4 22 sequence alignment experimental_method The sequence alignment is given in Supplementary Fig. S1, with the key metal-binding residues and those which give rise to quinolone resistance highlighted. RESULTS | |
| 71 93 metal-binding residues site The sequence alignment is given in Supplementary Fig. S1, with the key metal-binding residues and those which give rise to quinolone resistance highlighted. RESULTS | |
| 15 27 levofloxacin chemical The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 35 48 K. pneumoniae species The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 126 129 DNA chemical The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 154 157 DNA chemical The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 171 184 cleavage site site The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 196 198 −1 residue_number The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 203 205 +1 residue_number The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 256 259 DNA chemical The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 300 313 S. pneumoniae species The binding of levofloxacin in the K. pneumoniae complex is shown in Figs. 2 ▸, 3 ▸ and 5 ▸ and is hemi-intercalated into the DNA and stacked against the DNA bases at the cleavage site (positions −1 and +1 of the four-base-pair staggered cut in the 34-mer DNA) which is similar to that found for the S. pneumoniae complex. RESULTS | |
| 44 57 K. pneumoniae species Fig. 5 ▸ presents side-by-side views of the K. pneumoniae and S. pneumoniae active sites which shows that levofloxacin binds in a very similar manner in these two complexes with extensive π–π stacking interaction between the bases and the drug. RESULTS | |
| 62 75 S. pneumoniae species Fig. 5 ▸ presents side-by-side views of the K. pneumoniae and S. pneumoniae active sites which shows that levofloxacin binds in a very similar manner in these two complexes with extensive π–π stacking interaction between the bases and the drug. RESULTS | |
| 76 88 active sites site Fig. 5 ▸ presents side-by-side views of the K. pneumoniae and S. pneumoniae active sites which shows that levofloxacin binds in a very similar manner in these two complexes with extensive π–π stacking interaction between the bases and the drug. RESULTS | |
| 106 118 levofloxacin chemical Fig. 5 ▸ presents side-by-side views of the K. pneumoniae and S. pneumoniae active sites which shows that levofloxacin binds in a very similar manner in these two complexes with extensive π–π stacking interaction between the bases and the drug. RESULTS | |
| 188 212 π–π stacking interaction bond_interaction Fig. 5 ▸ presents side-by-side views of the K. pneumoniae and S. pneumoniae active sites which shows that levofloxacin binds in a very similar manner in these two complexes with extensive π–π stacking interaction between the bases and the drug. RESULTS | |
| 4 20 methylpiperazine chemical The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 51 60 quinolone chemical The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 136 142 Glu474 residue_name_number The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 147 153 Glu475 residue_name_number The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 158 171 S. pneumoniae species The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 184 190 Gln460 residue_name_number The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 195 201 Glu461 residue_name_number The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 206 219 K. pneumoniae species The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 231 247 glutamate at 474 residue_name_number The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 268 284 glutamine at 460 residue_name_number The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 292 302 Klebsiella taxonomy_domain The methylpiperazine at C7 (using the conventional quinolone numbering; C9 in the IUPAC numbering) on the drug extends towards residues Glu474 and Glu475 for S. pneumoniae and towards Gln460 and Glu461 for K. pneumoniae, where the glutamate at 474 is substituted by a glutamine at 460 in the Klebsiella strain. RESULTS | |
| 19 32 S. pneumoniae species Interestingly, for S. pneumoniae we observe only one possible orientation of the C7 groups in both subunits, while for K. pneumoniae we can see two: one with the same orientation as in S. pneumoniae and other rotated 180° away. RESULTS | |
| 120 133 K. pneumoniae species Interestingly, for S. pneumoniae we observe only one possible orientation of the C7 groups in both subunits, while for K. pneumoniae we can see two: one with the same orientation as in S. pneumoniae and other rotated 180° away. RESULTS | |
| 186 199 S. pneumoniae species Interestingly, for S. pneumoniae we observe only one possible orientation of the C7 groups in both subunits, while for K. pneumoniae we can see two: one with the same orientation as in S. pneumoniae and other rotated 180° away. RESULTS | |
| 32 39 crystal evidence They both exist within the same crystal in the two different dimers in the asymmetric unit. RESULTS | |
| 61 67 dimers oligomeric_state They both exist within the same crystal in the two different dimers in the asymmetric unit. RESULTS | |
| 36 40 ParE protein The side chains surrounding them in ParE are quite disordered and are more defined in K. pneumoniae (even though this complex is at lower resolution) than in S. pneumoniae. RESULTS | |
| 86 99 K. pneumoniae species The side chains surrounding them in ParE are quite disordered and are more defined in K. pneumoniae (even though this complex is at lower resolution) than in S. pneumoniae. RESULTS | |
| 158 171 S. pneumoniae species The side chains surrounding them in ParE are quite disordered and are more defined in K. pneumoniae (even though this complex is at lower resolution) than in S. pneumoniae. RESULTS | |
| 20 34 hydrogen bonds bond_interaction There are no direct hydrogen bonds from the drug to these residues (although it is possible that some are formed through water, which cannot be observed at this resolution). RESULTS | |
| 121 126 water chemical There are no direct hydrogen bonds from the drug to these residues (although it is possible that some are formed through water, which cannot be observed at this resolution). RESULTS | |
| 20 24 ParE protein Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 81 91 PD 0305970 chemical Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 107 120 S. pneumoniae species Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 121 124 DNA chemical Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 140 150 PD 0305970 chemical Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 159 172 hydrogen bond bond_interaction Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 176 180 ParE protein Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 189 195 Asp475 residue_name_number Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 216 222 Asp474 residue_name_number Obviously, the drug–ParE interaction in this region is less strong compared with PD 0305970 binding to the S. pneumoniae DNA complex, where PD 0305970 forms a hydrogen bond to ParE residue Asp475 and can form one to Asp474 if the bond rotates (Laponogov et al., 2010). RESULTS | |
| 51 63 levofloxacin chemical This may explain why drug-resistance mutations for levofloxacin are more likely to form in the ParC subunits rather than in the ParE subunits. RESULTS | |
| 95 99 ParC protein This may explain why drug-resistance mutations for levofloxacin are more likely to form in the ParC subunits rather than in the ParE subunits. RESULTS | |
| 128 132 ParE protein This may explain why drug-resistance mutations for levofloxacin are more likely to form in the ParC subunits rather than in the ParE subunits. RESULTS | |
| 30 34 Mg2+ chemical For both complexes there is a Mg2+ ion bound to levofloxacin between the carbonyl group at position 4 of the quinolone and the carboxyl at position 6 (Figs. 2 ▸ and 5 ▸ and Supplementary Fig. 2 ▸). RESULTS | |
| 39 47 bound to protein_state For both complexes there is a Mg2+ ion bound to levofloxacin between the carbonyl group at position 4 of the quinolone and the carboxyl at position 6 (Figs. 2 ▸ and 5 ▸ and Supplementary Fig. 2 ▸). RESULTS | |
| 48 60 levofloxacin chemical For both complexes there is a Mg2+ ion bound to levofloxacin between the carbonyl group at position 4 of the quinolone and the carboxyl at position 6 (Figs. 2 ▸ and 5 ▸ and Supplementary Fig. 2 ▸). RESULTS | |
| 109 118 quinolone chemical For both complexes there is a Mg2+ ion bound to levofloxacin between the carbonyl group at position 4 of the quinolone and the carboxyl at position 6 (Figs. 2 ▸ and 5 ▸ and Supplementary Fig. 2 ▸). RESULTS | |
| 4 17 S. pneumoniae species For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 18 34 topoisomerase IV complex_assembly For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 74 79 Asp83 residue_name_number For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 99 103 Mg2+ chemical For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 122 138 hydrogen-bonding bond_interaction For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 168 172 Mg2+ chemical For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 185 190 water chemical For S. pneumoniae topoisomerase IV, one of the O atoms of the carboxyl of Asp83 points towards the Mg2+ ion and is within hydrogen-bonding distance (5.04 Å) through an Mg2+-coordinated water. RESULTS | |
| 4 17 K. pneumoniae species For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 72 76 Mg2+ chemical For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 164 170 dimers oligomeric_state For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 178 191 K. pneumoniae species For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 192 199 crystal evidence For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 255 258 DNA chemical For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 269 273 ParE protein For K. pneumoniae both of the carboxyl O atoms are pointing towards the Mg2+ ion at distances of 4.86 and 4.23 Å. These residues are ordered in only one of the two dimers in the K. pneumoniae crystal (the one in which the C7 group is pointing towards the DNA away from ParE, although the conformations of these two groups on the drug are probably not correlated). RESULTS | |
| 4 20 topoisomerase IV complex_assembly The topoisomerase IV ParE27-ParC55 fusion protein from K. pneumoniae was fully active in promoting levofloxacin-mediated cleavage of DNA (Fig. 6 ▸). RESULTS | |
| 21 34 ParE27-ParC55 complex_assembly The topoisomerase IV ParE27-ParC55 fusion protein from K. pneumoniae was fully active in promoting levofloxacin-mediated cleavage of DNA (Fig. 6 ▸). RESULTS | |
| 55 68 K. pneumoniae species The topoisomerase IV ParE27-ParC55 fusion protein from K. pneumoniae was fully active in promoting levofloxacin-mediated cleavage of DNA (Fig. 6 ▸). RESULTS | |
| 99 111 levofloxacin chemical The topoisomerase IV ParE27-ParC55 fusion protein from K. pneumoniae was fully active in promoting levofloxacin-mediated cleavage of DNA (Fig. 6 ▸). RESULTS | |
| 133 136 DNA chemical The topoisomerase IV ParE27-ParC55 fusion protein from K. pneumoniae was fully active in promoting levofloxacin-mediated cleavage of DNA (Fig. 6 ▸). RESULTS | |
| 7 17 absence of protein_state In the absence of the drug and ATP, the protein converted supercoiled pBR322 into a ladder of bands corresponding to relaxed DNA. RESULTS | |
| 22 26 drug chemical In the absence of the drug and ATP, the protein converted supercoiled pBR322 into a ladder of bands corresponding to relaxed DNA. RESULTS | |
| 31 34 ATP chemical In the absence of the drug and ATP, the protein converted supercoiled pBR322 into a ladder of bands corresponding to relaxed DNA. RESULTS | |
| 125 128 DNA chemical In the absence of the drug and ATP, the protein converted supercoiled pBR322 into a ladder of bands corresponding to relaxed DNA. RESULTS | |
| 17 29 levofloxacin chemical The inclusion of levofloxacin produced linear DNA in a dose-dependent and ATP-independent fashion. RESULTS | |
| 46 49 DNA chemical The inclusion of levofloxacin produced linear DNA in a dose-dependent and ATP-independent fashion. RESULTS | |
| 74 77 ATP chemical The inclusion of levofloxacin produced linear DNA in a dose-dependent and ATP-independent fashion. RESULTS | |
| 39 52 S. pneumoniae species Similar behaviour was observed for the S. pneumoniae topoisomerase IV ParE30-ParC55 fusion protein. RESULTS | |
| 53 70 topoisomerase IV complex_assembly Similar behaviour was observed for the S. pneumoniae topoisomerase IV ParE30-ParC55 fusion protein. RESULTS | |
| 71 84 ParE30-ParC55 complex_assembly Similar behaviour was observed for the S. pneumoniae topoisomerase IV ParE30-ParC55 fusion protein. RESULTS | |
| 4 8 CC25 evidence The CC25 (the drug concentration that converted 25% of the supercoiled DNA substrate to a linear form) was 0.5 µM for the Klebsiella enzyme and 1 µM for the pneumococcal enzyme. RESULTS | |
| 71 74 DNA chemical The CC25 (the drug concentration that converted 25% of the supercoiled DNA substrate to a linear form) was 0.5 µM for the Klebsiella enzyme and 1 µM for the pneumococcal enzyme. RESULTS | |
| 122 132 Klebsiella taxonomy_domain The CC25 (the drug concentration that converted 25% of the supercoiled DNA substrate to a linear form) was 0.5 µM for the Klebsiella enzyme and 1 µM for the pneumococcal enzyme. RESULTS | |
| 157 169 pneumococcal taxonomy_domain The CC25 (the drug concentration that converted 25% of the supercoiled DNA substrate to a linear form) was 0.5 µM for the Klebsiella enzyme and 1 µM for the pneumococcal enzyme. RESULTS | |
| 15 28 K. pneumoniae species Interestingly, K. pneumoniae strains are much more susceptible to levofloxacin than S. pneumoniae, with typical MIC values of 0.016 and 1 mg l−1, respectively (Odenholt & Cars, 2006), reflecting differences in multiple factors (in addition to binding affinity) that influence drug responses, including membrane, peptidoglycan structure, drug-uptake and efflux mechanisms. RESULTS | |
| 66 78 levofloxacin chemical Interestingly, K. pneumoniae strains are much more susceptible to levofloxacin than S. pneumoniae, with typical MIC values of 0.016 and 1 mg l−1, respectively (Odenholt & Cars, 2006), reflecting differences in multiple factors (in addition to binding affinity) that influence drug responses, including membrane, peptidoglycan structure, drug-uptake and efflux mechanisms. RESULTS | |
| 84 97 S. pneumoniae species Interestingly, K. pneumoniae strains are much more susceptible to levofloxacin than S. pneumoniae, with typical MIC values of 0.016 and 1 mg l−1, respectively (Odenholt & Cars, 2006), reflecting differences in multiple factors (in addition to binding affinity) that influence drug responses, including membrane, peptidoglycan structure, drug-uptake and efflux mechanisms. RESULTS | |
| 243 259 binding affinity evidence Interestingly, K. pneumoniae strains are much more susceptible to levofloxacin than S. pneumoniae, with typical MIC values of 0.016 and 1 mg l−1, respectively (Odenholt & Cars, 2006), reflecting differences in multiple factors (in addition to binding affinity) that influence drug responses, including membrane, peptidoglycan structure, drug-uptake and efflux mechanisms. RESULTS | |
| 19 35 topoisomerase IV complex_assembly Moreover, although topoisomerase IV is primarily the target of levofloxacin in S. pneumoniae, it is likely to be gyrase in the Gram-negative K. pneumoniae. RESULTS | |
| 63 75 levofloxacin chemical Moreover, although topoisomerase IV is primarily the target of levofloxacin in S. pneumoniae, it is likely to be gyrase in the Gram-negative K. pneumoniae. RESULTS | |
| 79 92 S. pneumoniae species Moreover, although topoisomerase IV is primarily the target of levofloxacin in S. pneumoniae, it is likely to be gyrase in the Gram-negative K. pneumoniae. RESULTS | |
| 113 119 gyrase protein_type Moreover, although topoisomerase IV is primarily the target of levofloxacin in S. pneumoniae, it is likely to be gyrase in the Gram-negative K. pneumoniae. RESULTS | |
| 127 140 Gram-negative taxonomy_domain Moreover, although topoisomerase IV is primarily the target of levofloxacin in S. pneumoniae, it is likely to be gyrase in the Gram-negative K. pneumoniae. RESULTS | |
| 141 154 K. pneumoniae species Moreover, although topoisomerase IV is primarily the target of levofloxacin in S. pneumoniae, it is likely to be gyrase in the Gram-negative K. pneumoniae. RESULTS | |
| 41 50 structure evidence In summary, we have determined the first structure of a quinolone–DNA cleavage complex involving a type II topoisomerase from K. pneumoniae. RESULTS | |
| 56 65 quinolone chemical In summary, we have determined the first structure of a quinolone–DNA cleavage complex involving a type II topoisomerase from K. pneumoniae. RESULTS | |
| 66 69 DNA chemical In summary, we have determined the first structure of a quinolone–DNA cleavage complex involving a type II topoisomerase from K. pneumoniae. RESULTS | |
| 99 121 type II topoisomerase protein_type In summary, we have determined the first structure of a quinolone–DNA cleavage complex involving a type II topoisomerase from K. pneumoniae. RESULTS | |
| 127 140 K. pneumoniae species In summary, we have determined the first structure of a quinolone–DNA cleavage complex involving a type II topoisomerase from K. pneumoniae. RESULTS | |
| 59 69 Klebsiella taxonomy_domain Given the current concerns about drug-resistant strains of Klebsiella, the structure reported here provides key information in understanding the action of currently used quinolones and should aid in the development of other topoisomerase-targeting therapeutics active against this major human pathogen. RESULTS | |
| 75 84 structure evidence Given the current concerns about drug-resistant strains of Klebsiella, the structure reported here provides key information in understanding the action of currently used quinolones and should aid in the development of other topoisomerase-targeting therapeutics active against this major human pathogen. RESULTS | |
| 170 180 quinolones chemical Given the current concerns about drug-resistant strains of Klebsiella, the structure reported here provides key information in understanding the action of currently used quinolones and should aid in the development of other topoisomerase-targeting therapeutics active against this major human pathogen. RESULTS | |
| 224 237 topoisomerase protein_type Given the current concerns about drug-resistant strains of Klebsiella, the structure reported here provides key information in understanding the action of currently used quinolones and should aid in the development of other topoisomerase-targeting therapeutics active against this major human pathogen. RESULTS | |
| 287 292 human species Given the current concerns about drug-resistant strains of Klebsiella, the structure reported here provides key information in understanding the action of currently used quinolones and should aid in the development of other topoisomerase-targeting therapeutics active against this major human pathogen. RESULTS | |
| 12 15 DNA chemical Protein and DNA used in the co-crystallization experiment. FIG | |
| 28 46 co-crystallization experimental_method Protein and DNA used in the co-crystallization experiment. FIG | |
| 55 70 crystallization experimental_method (a) Coloured diagram of the protein constructs used in crystallization. FIG | |
| 4 7 DNA chemical (b) DNA sequences used in crystallization. FIG | |
| 26 41 crystallization experimental_method (b) DNA sequences used in crystallization. FIG | |
| 22 34 levofloxacin chemical Chemical structure of levofloxacin (a) and its conformations observed within the active sites of S. pneumoniae topoisomerase IV (b) and K. pneumoniae topoisomerase IV (c, d). FIG | |
| 81 93 active sites site Chemical structure of levofloxacin (a) and its conformations observed within the active sites of S. pneumoniae topoisomerase IV (b) and K. pneumoniae topoisomerase IV (c, d). FIG | |
| 97 110 S. pneumoniae species Chemical structure of levofloxacin (a) and its conformations observed within the active sites of S. pneumoniae topoisomerase IV (b) and K. pneumoniae topoisomerase IV (c, d). FIG | |
| 111 127 topoisomerase IV complex_assembly Chemical structure of levofloxacin (a) and its conformations observed within the active sites of S. pneumoniae topoisomerase IV (b) and K. pneumoniae topoisomerase IV (c, d). FIG | |
| 136 149 K. pneumoniae species Chemical structure of levofloxacin (a) and its conformations observed within the active sites of S. pneumoniae topoisomerase IV (b) and K. pneumoniae topoisomerase IV (c, d). FIG | |
| 150 166 topoisomerase IV complex_assembly Chemical structure of levofloxacin (a) and its conformations observed within the active sites of S. pneumoniae topoisomerase IV (b) and K. pneumoniae topoisomerase IV (c, d). FIG | |
| 0 21 Electron-density maps evidence Electron-density maps (2F obs − F calc) are shown as meshes for the drug molecules contoured at 1.5σ and are limited to a distance of 2.3 Å from the drug atoms. FIG | |
| 52 68 topoisomerase IV complex_assembly Overall orthogonal views of the cleavage complex of topoisomerase IV from K. pneumoniae in surface (left) and cartoon (right) representations. FIG | |
| 74 87 K. pneumoniae species Overall orthogonal views of the cleavage complex of topoisomerase IV from K. pneumoniae in surface (left) and cartoon (right) representations. FIG | |
| 4 8 ParC protein The ParC subunit is in blue, ParE is in yellow and DNA is in cyan. FIG | |
| 29 33 ParE protein The ParC subunit is in blue, ParE is in yellow and DNA is in cyan. FIG | |
| 51 54 DNA chemical The ParC subunit is in blue, ParE is in yellow and DNA is in cyan. FIG | |
| 4 9 bound protein_state The bound quinolone molecules (levofloxacin) are in red and are shown using van der Waals representation. FIG | |
| 10 19 quinolone chemical The bound quinolone molecules (levofloxacin) are in red and are shown using van der Waals representation. FIG | |
| 31 43 levofloxacin chemical The bound quinolone molecules (levofloxacin) are in red and are shown using van der Waals representation. FIG | |
| 51 73 type II topoisomerases protein_type Schematic representation of the catalytic cycle of type II topoisomerases. FIG | |
| 4 8 ParC protein The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 28 34 ParC55 protein The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 52 56 ParC protein The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 68 86 β-pinwheel domain structure_element The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 105 109 ParE protein The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 121 134 ATPase domain structure_element The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 150 154 ParE protein The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 155 172 C-terminal domain structure_element The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 174 180 ParE30 protein The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 200 206 G-gate structure_element The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 207 210 DNA chemical The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 231 240 T-segment structure_element The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 241 244 DNA chemical The ParC N-terminal domain (ParC55) is in grey, the ParC C-terminal β-pinwheel domain is in silver, the ParE N-terminal ATPase domain is in red, the ParE C-terminal domain (ParE30) is in yellow, the G-gate DNA is in green and the T-segment DNA is in purple. FIG | |
| 0 5 Bound protein_state Bound ATP is indicated by pink circles in the ATPase domains (reproduced with permission from Fig. 1 of Lapanogov et al., 2013). FIG | |
| 6 9 ATP chemical Bound ATP is indicated by pink circles in the ATPase domains (reproduced with permission from Fig. 1 of Lapanogov et al., 2013). FIG | |
| 46 60 ATPase domains structure_element Bound ATP is indicated by pink circles in the ATPase domains (reproduced with permission from Fig. 1 of Lapanogov et al., 2013). FIG | |
| 22 34 active sites site Detailed views of the active sites of topoisomerase IV from S. pneumoniae and K. pneumoniae with quinolone molecules bound. FIG | |
| 38 54 topoisomerase IV complex_assembly Detailed views of the active sites of topoisomerase IV from S. pneumoniae and K. pneumoniae with quinolone molecules bound. FIG | |
| 60 73 S. pneumoniae species Detailed views of the active sites of topoisomerase IV from S. pneumoniae and K. pneumoniae with quinolone molecules bound. FIG | |
| 78 91 K. pneumoniae species Detailed views of the active sites of topoisomerase IV from S. pneumoniae and K. pneumoniae with quinolone molecules bound. FIG | |
| 97 106 quinolone chemical Detailed views of the active sites of topoisomerase IV from S. pneumoniae and K. pneumoniae with quinolone molecules bound. FIG | |
| 117 122 bound protein_state Detailed views of the active sites of topoisomerase IV from S. pneumoniae and K. pneumoniae with quinolone molecules bound. FIG | |
| 4 13 magnesium chemical The magnesium ions and their coordinating amino acids are shown in purple. FIG | |
| 4 15 active-site site The active-site tyrosine and arginine are in orange. FIG | |
| 16 24 tyrosine residue_name The active-site tyrosine and arginine are in orange. FIG | |
| 29 37 arginine residue_name The active-site tyrosine and arginine are in orange. FIG | |
| 4 7 DNA chemical The DNA is shown in silver/cyan. FIG | |
| 4 8 ParC protein The ParC and ParE backbones are shown in blue and yellow, respectively. FIG | |
| 13 17 ParE protein The ParC and ParE backbones are shown in blue and yellow, respectively. FIG | |
| 14 17 DNA chemical Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 30 46 topoisomerase IV complex_assembly Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 52 61 ParE-ParC complex_assembly Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 83 96 K. pneumoniae species Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 98 100 KP species Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 106 119 S. pneumoniae species Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 121 123 SP species Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 137 149 levofloxacin chemical Comparison of DNA cleavage by topoisomerase IV core ParE-ParC fusion proteins from K. pneumoniae (KP) and S. pneumoniae (SP) promoted by levofloxacin. FIG | |
| 55 71 topoisomerase IV complex_assembly Supercoiled plasmid pBR322 (400 ng) was incubated with topoisomerase IV proteins (400 ng) in the absence or presence of levofloxacin at the indicated concentrations. FIG | |
| 108 119 presence of protein_state Supercoiled plasmid pBR322 (400 ng) was incubated with topoisomerase IV proteins (400 ng) in the absence or presence of levofloxacin at the indicated concentrations. FIG | |
| 120 132 levofloxacin chemical Supercoiled plasmid pBR322 (400 ng) was incubated with topoisomerase IV proteins (400 ng) in the absence or presence of levofloxacin at the indicated concentrations. FIG | |
| 109 112 DNA chemical After 60 min incubation, samples were treated with SDS and proteinase K to remove proteins covalent bound to DNA, and the DNA products were examined by gel electrophoresis in 1% agarose. FIG | |
| 122 125 DNA chemical After 60 min incubation, samples were treated with SDS and proteinase K to remove proteins covalent bound to DNA, and the DNA products were examined by gel electrophoresis in 1% agarose. FIG | |
| 27 30 DNA chemical Lane A, supercoiled pBR322 DNA; N, L and S, nicked, linear and supercoiled pBR322, respectively. FIG | |