bluuebunny/crossref_metadata_2025_split huggingface dataset:
4‐Hydroxybutyryl‐CoADehydratase
Authors: Martins Berta M. , Messerschmidt Albrecht , Friedrich Peter , Zhang Jin , Buckel Wolfgang 
Published: December 2011

AbstractDehydratases catalyze the cleavage of a carbon–oxygen bond yielding an unsaturated product via α,β‐elimination of water. The α‐hydrogen (pK ∼ 8) to be removed as proton is activated by an adjacent electron‐withdrawing group, and the hydroxyl group leaves from the β‐position. In contrast, anaerobic organisms possess 2‐ or 4‐hydroxyacyl‐CoA dehydratases that use radicals to lower the pKof the unactivated β‐carbons by 26 units. An example is 4‐hydroxybutyryl‐CoA dehydratase (4‐BUDH) fromClostridium aminobutyricumthat interconverts 4‐hydroxybutyryl‐CoA to crotonyl‐CoA. 4‐BUDH is functional as a homotetramer with two active sites per dimer and displays a distinctive active site architecture with the [4Fe–4S]2+cluster, coordinated by three cysteine and one histidine residues, located 7 Å from theRe‐side of the flavin adenine dinucleotide (FAD). Albeit requiring the cluster and an oxidized FAD for catalysis, the overall reaction occurs with no net redox change. The unexpected structural relation of 4‐BUDH with medium chain acyl‐CoA dehydrogenases suggests a radical‐based mechanism for both flavoproteins. The biochemical and structural characterization of 4‐BUDH is an important step toward a detailed study of the structural bases how enzymes regulate the generation and reactivity of radical species at a molecular level, which is a fundamental but still poorly understood problem.
Human Ferrochelatase
Authors: Lanzilotta William N , Dailey Harry A 
Published: December 2011

AbstractFerrochelatase catalyzes the terminal step of heme biosynthesis, the insertion of ferrous iron into protoporphyrin IX to form heme. The mammalian enzyme is a homodimer with a total molecular weight of 83 000 and is associated with the matrix side of the inner mitochondrial membrane. Each subunit contains a [2Fe–2S] cluster whose coordination and spectral properties are unlike any other currently characterized [2Fe–2S] cluster. The crystal structure of the human enzyme both with and without porphyrin substrate‐bound is presented and discussed. The enzyme without substrate‐bound possesses an open mouth for an active site with the two lips of the mouth being responsible for interaction with the membrane. The enzyme with bound porphyrin has a closed mouth that results in a hand‐in‐glove fit with the porphyrin substrate.
Flavodiiron Proteins: Nitric Oxide and/or Oxygen Reductases
Authors: Vicente João B , Carrondo Maria Arménia , Teixeira Miguel , Frazão Carlos 
Published: December 2011

AbstractFlavodiiron proteins (FDPs) have been isolated from and identified in genomes of bacteria, archaea, and a restricted group of pathogenic protozoa, mostly anaerobes or microaerophiles. The current knowledge on this protein family suggests alternative or complementary roles in nitric oxide (NO) and/or oxygen detoxification in anaerobes. These enzymes couple substrate (NO, O2) reduction to the oxidation of NAD(P)H or F420H2through electron transfer chains with varying complexity. The first crystallographic structure of an FDP, theDesulfovibrio gigasrubredoxin:oxygen oxidoreductase (Dg_ROO), revealed the structural prototype of this family and the identification of common amino acid sequence motifs. The common functional unit of the FDP family is a ‘head‐to‐tail’ homodimer, each monomer comprising two structural domains: an N‐terminal metallo‐β‐lactamase‐like domain, where a nonheme diiron center is embedded (being the active site of NO/O2reduction), and a C‐terminal flavodoxin‐like domain, harboring a flavin mononucleotide (FMN) moiety. The homodimer ‘head‐to‐tail’ arrangement places the diiron from each monomer in close proximity with the FMN from its opposing monomer, allowing efficient electron transfer between cofactors, otherwise impaired by their large distance within the same monomer.Herein are summarized structural and functional features of FDPs from several organisms, which provide clues to an understanding of their role in microbial nitrosative and/or oxidative stress resistance.
Glutamate CarboxypeptidaseII
Authors: Mesters Jeroen R , Hilgenfeld Rolf 
Published: December 2011

AbstractGlutamate carboxypeptidase II (GCP II) is a homodimeric, dinuclear zinc carboxypeptidase that catalyzes the cleavage of two endogenous substrates carryingL‐glutamate at the C‐terminal P1′ position, namelyN‐acetyl‐L‐aspartyl‐α‐L‐glutamate (α‐NAAG) and folylpoly‐γ‐L‐glutamate (folylpolyglutamate). Former synonyms for GCP II, a type‐II membrane glycoprotein that belongs to the transferrin receptor family of proteins, include prostate‐specific membrane antigen (PSMA), folylpoly‐γ‐glutamate carboxypeptidase (FGCP), andN‐acetylated α‐linked acidic dipeptidase (NAALADase). GCP II predominantly occurs in nearly all types of glial cells and is drastically overproduced in endothelial cells of tumor‐associated neovasculature and in prostate cancer tissue. The particular role of PSMA, a folylpolyglutamate hydrolase, in prostate cancer is poorly understood. In the brain, GCP II catalyzes the cleavage of the abundant neuropeptide α‐NAAG that acts as an agonist for the metabotropic (i.e. G‐protein‐coupled) glutamate receptor‐3 (mGluR3), and as a mixed agonist/antagonist forN‐methyl‐D‐aspartate (NMDA) receptors. The liberatedL‐glutamate acts as a downstream neurotransmitter that is excitotoxic at high concentrations, harming retina and brain. Accordingly, inhibitory compounds of GCP II have been shown to provide neuroprotection. In addition, they may prove useful, through the binding to PSMA, for the imaging and possible treatment of certain forms of cancer.
Nitrogenase: Recent Advances
Authors: Andrade Susana LA , Hu Yilin , Ribbe Markus W , Einsle Oliver 
Published: December 2011

AbstractNitrogenase catalyzes the reductive fixation of nitrogen from atmospheric N2for biological syntheses, and as such it constitutes the only enzyme known to be able to cleave the highly stable triple bond of the dinitrogen molecule. Structures are known of both component proteins of nitrogenase, the enzymatically active MoFe protein and its electron donor, the Fe protein. In spite of a wealth of biochemical and biophysical data on nitrogenase, the mechanistic details of its action remain poorly understood. This article provides an update on recent results in nitrogenase research, including the discovery of a central, light atom in the center of the FeMo cofactor, studies on substrate binding to the cofactor in mutant proteins, and novel aspects of complex formation between both component proteins. Particular emphasis is given to the significant progress made in understanding the biosynthesis of the complex metal clusters of the MoFe protein, the P‐cluster and the FeMo cofactor.
Ribonucleotide Reductase: Recent Advances
Authors: Stubbe JoAnne , Cotruvo Joseph A 
Published: December 2011

AbstractRibonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides and play an essential role in nucleic acid metabolism in all organisms. RNRs have been divided into three classes. They share a structurally homologous subunit where the reduction occurs, with the chemistry being initiated by thiyl radical‐mediated abstraction of the nucleotide's 3′‐hydrogen atom. The classification of RNRs is based on the different strategies used to generate the transient thiyl radical. The class Ia and Ib RNRs use a diferric‐tyrosyl radical cofactor, the class II RNRs use adenosylcobalamin, and the class III RNRs use a glycyl radical generated by a [4Fe4S]1+cluster andS‐adenosylmethionine. This article focuses on the recent advances in our understanding of thein vitroandin vivomechanisms of formation of the metallocofactors in the class I RNRs inE. coliandS. cerevisiae. The discovery of a new class of RNR, class Ic, whose active cofactor is proposed to be an MnIVFeIIIcluster, and a summary of recent insights into the chemistry of the novel cofactor are also described. Finally, the current understanding of the unprecedented role of the metallocofactor in radical propagation over 35 Å in the class Ia—and presumably class Ib and Ic—RNRs is presented.
TheMre11 Nuclease Complex
Authors: Hopfner Karl‐Peter , Bemeleit Derk , Lammens Katja 
Published: December 2011

AbstractThe repair of DNA double‐strand breaks (DSBs) is necessary to maintain genome stability and prevent cell aberration and cancer development. Meiotic recombination 11 (Mre11) and radiation sensitivity 50 (Rad50) form an evolutionary conserved complex (denoted Mre11 complex) that is a key factor in the detection, repair, and signaling of DSBs. The Mre11 complex possesses ATP‐stimulated DNA binding, DNA endo‐ and exonuclease activities as well as DNA cross‐linking functions. The Mre11 complex is a primary sensor for DNA DSBs and is involved in many aspects of the repair of and cellular response to DNA DSBs. Its activity is controlled by at least three different metal binding sites, a manganese‐dependent nuclease (Mre11 phosphodiesterase domain), a magnesium‐dependent ATPase (Rad50 ABC ATPase domain), and a zinc‐mediated DNA tethering function, located at the apex of a long Rad50 coiled‐coil domain. Although the mechanism remains to be shown, current structural and functional data indicate that the Mre11 complex is an ATP‐dependent cross‐linker and a processing factor for DNA ends.
Acetylene Hydratase
Authors: Seiffert Grazyna B , Abt Dietmar , tenBrink Felix , Fischer David , Einsle Oliver , Kroneck Peter MH 
Published: December 2011

AbstractThe tungsten‐iron‐sulfur enzyme acetylene hydratase is a rather unique enzyme within the class of tungsten/molybdenum enzymes in the sense that it catalyzes a nonredox reaction, the addition of one molecule of water to the CC bond of acetylene to form acetaldehyde. Its crystal structure (1.26 Å) reveals a close to octahedral, or trigonalantiprismatic tungsten center, which binds a water molecule that gets activated by an adjacent aspartate residue such that it can attack an acetylene molecule bound in a distinct, hydrophobic pocket. This requires a strong shift of pKaof the aspartate, caused by a nearby low‐potential [4Fe–4S] cluster. To gain access to this novel W‐Asp‐active site, the protein evolved a new substrate channel distant from where it is found in other molybdenum and tungsten enzymes.
VAP1—Snake Venom Homolog of MammalianADAMs
Authors: Takeda Soichi 
Published: December 2011

AbstractVascular‐apoptosis‐inducing protein‐1 (VAP1) is a zinc endopeptidase from western diamondback snakeCrotalus atroxvenom. VAP1 possesses a metalloproteinase/disintegrin/cysteine‐rich (MDC) domain that bears the typical domain architecture of the adamalysin/reprolysin/ADAM (a disintegrin and metalloproteinase) family of proteins. Mammalian ADAM proteinases are unique in that they have both proteolytic and adhesive properties. Additionally, as cell‐surface proteins, they constitute a major class of membrane‐anchored sheddases and participate in the processing of cell‐surface‐protein ectodomains, including the latent forms of growth factors, cytokines, and receptors. The crystal structures of VAP1 reveal a C‐shaped MDC domain architecture and a potential protein–protein interaction site in the C domain that faces the catalytic site in the M domain. The structures of VAP1 and related proteins suggest that there is interplay between proteolytic and adhesive functions in the proteinases of the adamalysin/reprolysin/ADAM family.
The
Mgt
E
Mg
2+
Transporter
Authors: Maguire Michael E 
Published: December 2011

Abstract

The MgtE class of Mg
2+
ion transporter is widespread in the bacteria, with over 50% of current genomic sequences and most marine metagenome sequences exhibiting a homolog. MgtE is the primary provider of cytosolic Mg
2+
in those organisms that carry it. MgtE homologs are widespread in the metazoa and fungi (SLC41 family) but apparently absent in the plants. In bacteria, MgtE functions as a Mg
2+
influx system, while in eukaryotes specific MgtE proteins may function as either influx or efflux systems. Despite their ubiquity, virtually nothing is known about the physiological role of MgtE. Bacterial MgtE proteins are homodimers, with the entire soluble domain at the N terminus and the entire membrane domain at the C terminus. A recent crystal structure of

Thermus thermophilus

MgtE putatively in the closed form shows that the membrane domain consists of 5 transmembrane helices, each at a substantial angle to the plane of the membrane, giving 10 transmembrane helices in the dimer. The pore is formed primarily by transmembrane segments 2 and 5. Each membrane domain is connected to the soluble domain by a single α‐helix orthogonal to the membrane. Attached to this ‘connecting helix’ is a soluble domain containing a superhelical bundle of 10 α‐helices (‘N domain’) followed by duplicated tandem cystathionine β‐synthase‐like motifs, which end in the ‘connecting helix.’ The N domain has structural homology to the FliG protein of the flagellar motor. It is not clear how Mg
2+
is recognized and selected. The crystal structure also contains several sites for bound Mg
2+
ions, one within the pore. Two Mg
2+
sites per monomer connect the ‘connecting helice’ and CBS domain to the membrane domain, while two additional sites per monomer connect the CBS‐ and N domains. The structure of the soluble domain with and without Mg
2+
has also been solved. The absence of Mg
2+
does not alter the structure of the N domain significantly, but the structure of the tandem cystathionine β‐synthase domains within each monomer does change to some extent. The largest change due to the absence of Mg
2+
is that the entire cystathionine β‐synthase domain rotates and slightly twists 120° from the N domain. It is not clear if this rotation is part of the mechanism by which the pore opens and closes. Presumably, the bound Mg
2+
ions in the soluble domain play a role in sensing Mg
2+
, and their dissociation could allow domain movement and lead to opening of the pore.
Mitochondrial Respiratory
C
omplex
II
Authors: Bartlam Mark , Sun Fei , Rao Zihe 
Published: December 2011

Abstract
The mitochondrial respiratory Complex II, or succinate : ubiquinone oxidoreductase (SQR), is an integral membrane protein complex in both the tricarboxylic acid cycle (Krebs cycle) and aerobic respiration. To date, X‐ray crystal structures of mitochondrial respiratory Complex II have been reported from porcine heart and from chicken, as well as the structures of a number of related bacterial SQR or quinol : fumarate oxidoreductase (QFR) structures. Complex II comprises of two hydrophilic proteins (flavoprotein (Fp) and iron–sulfur protein (Ip)) and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. A proximal ubiquinone site (Qp) is located on the matrix side of the protein complex. Inhibitor‐bound structures using 3‐nitropropionate (NPA), 2‐thenoyltrifluoroacetone (TTFA), and carboxin provide further functional details for Complex II. NPA, a succinate analog, confirms the location of the succinate binding site. TTFA, a classical inhibitor for the ubiquinone reduction of Complex II that works by occupying its ubiquinone binding sites, confirms the location of the Qp site in both porcine heart and chicken structures. The available Complex II structures provide models for studying the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.
Zinc‐Binding Protein
Znu
A
Authors: Smith Thomas J , Pakrasi Himadri B 
Published: December 2011

Abstract

ZnuA is a high‐affinity, periplasmic zinc (Zn
2+
)‐binding protein that is a component of a three‐protein ABC transport system. The overall structure of ZnuA is very similar to the previously determined structures of the periplasmic domains of the ABC metal transporters PsaA and TroA. ZnuA has a ‘C clamp’ shape, which is composed of two (β/α)
4
domains related by pseudo twofold symmetry. Also like the other metal transporters, the two domains are linked by a 33‐residue α‐helix. This likely keeps the two domains in a relatively fixed position as made evident by the lack of large domain movement upon binding and release of metal. Unlike PsaA and TroA, however, there is an extended loop near the metal‐binding cleft, which is rich in histidines and acidic residues. Structural studies demonstrate that the removal of this loop does not affect the structure of ZnuA, and isothermal titration calorimetry (ITC) studies show that this loop contains low‐affinity zinc‐binding sites but does not directly affect the binding of zinc to the high‐affinity site within the cleft. Together, these results suggest that this unusual loop region may play a role in the regulation of zinc uptake when the periplasmic concentration of zinc is high.
Siderophore‐Binding Periplasmatic ProteinFhuDand Related Periplasmic Binding Proteins Involved in Bacterial Iron Uptake
Authors: Krewulak Karla D. , Köster Wolfgang , Vogel Hans J. 
Published: December 2011

AbstractTo fulfill their nutritional requirement for iron, many microorganisms synthesize low‐molecular‐weight iron‐chelating compounds calledsiderophores. These iron sources are transported into the gram‐negative bacterial cellviaspecific uptake pathways that include an outer membrane receptor, a periplasmic binding protein (PBP), and an inner membrane ATP‐binding cassette (ABC) transporter. Gram‐positive bacteria lack an outer membrane, and thus the uptake of the ferric siderophore involves a membrane‐anchored PBP and an ABC transporter. Siderophores are classified as hydroxamate, catecholate, or hydroxycarboxylate type siderophores. This review details what is currently known about the PBP, FhuD (Fhu — ferric hydroxamate uptake), involved in the uptake of hydroxamate‐type siderophores. In addition, several structurally related periplasmic binding proteins that mediate bacterial metal ion transport are also discussed.
Human FactorVIII
Authors: Ki Ngo Jacky Chi , Huang Mingdong , Roth David A. , Furie Barbara C. , Furie Bruce 
Published: December 2011

AbstractFactor VIII is a critical blood clotting factor, which forms a complex with the serine protease factor IXa upon activation to convert factor X to factor Xa, which in turn activates thrombin. Deficiency or dysfunction of the protein leads to hemophilia A, a common X‐linked disorder. Structures of two different constructs of factor VIII have been determined by X‐ray crystallography at intermediate resolutions. Both structures show that the protein is composed of five globular domains and contains binding sites for calcium and copper ions, which are important in the regulation of factor VIII structure and activity. The three A domains, each consists of two β‐barrel structures that resemble the cupredoxin fold, are structurally homologous with one other. The two homologous C domains are defined by a distorted β‐barrel and reveal membrane‐binding features. Comparison of the two crystal structures has revealed structural differences between the two constructs and provides new perspectives for understanding the activation of factor VIII and the role of metal ions in the regulation of factor VIII activity.
Dissimilatory Adenosine‐5′‐Phosphosulfate Reductase
Authors: Schiffer Alexander , Fritz Günter , Büchert Thomas , Herrmanns Karolin , Steuber Julia , Ermler Ulrich , Kroneck Peter MH 
Published: December 2011

AbstractThe iron‐sulfur flavoenzyme adenosine‐5′‐phosphosulfate reductase (APSR) catalyzes the reductive cleavage of APS (adenosine‐5′‐phosphosulfate) to sulfite plus AMP and the reverse reaction, both important reactions within the biogeochemical sulfur cycle. The structure of the dissimilatory enzyme from the hyperthermophilic sulfate reducerArchaeoglobus fulgidusat 1.6 Å resolution reveals APSR as heterotetrameric α2ß2complex; however, the αß heterodimer is the functionally active unit. The FAD(flavin adenine dinucleotide) binding α‐subunit of APSR is structurally similar to the corresponding subunit of fumarate reductases, suggesting a common ancestor that resembles archaeal APSR. A clear separation is observed between the electron transfer process that extends over 25 Å from the protein surface via two [4Fe‐4S] clusters to thesi‐side of FAD and the chemical process of APS reduction at there‐side of FAD. The structures of APSR complex with the substrates APS, sulfite, and AMP trapped the enzyme in four different states and allowed, together with information from spectroscopic studies, to develop a detailed picture of the catalytic cycle. The nucleophilic attack of the N5 atom of FADH−onto the sulfur of APS, both negatively charged, proceeds in a compressed enzyme‐substrate complex relaxed in the formed FAD‐APS and FAD‐sulfite adducts.
Dissimilatory Sulfite Reductase
Authors: Parey Kristian , Schiffer Alexander , Steuber Julia , Fritz Günter , Ermler Ulrich , Kroneck Peter MH 
Published: December 2011

AbstractDissimilatory sulfite reductase (dSiR) belongs to the group of oxidoreductases and is a key enzyme of the biogeochemical sulfur cycle. The enzyme is organized as a heterotetrameric α2β2, or a heterohexameric α2β2γ2complex, and catalyzes the reduction of sulfite (SO32−) to hydrogen sulfide (H2S) in a six‐electron transfer process as the final step of dissimilatory sulfate reduction. Thiosulfate (S2O32−) and trithionate (S3O62−) have been postulated as potential intermediates in this energy conserving process, which evolved in an early stage of prokaryotic life in an anoxic environment. Like assimilatory sulfite reductase (aSiR), dSiR also reduces nitrite to ammonia. Sulfite reductases and related nitrite reductases are the only known class of enzymes that couple a siroheme (an iron‐tetrahydroporphyrin of the isobacteriochlorin class) to an iron–sulfur cluster to construct a catalytically active redox center.
Arsenite Oxidase
Authors: Hille Russ 
Published: December 2011

Abstract
The crystal structure of arsenite oxidase has been determined, and the enzyme found to represent a new subclass of the dimethyl sulfoxide (DMSO) reductase family of molybdenum‐containing enzymes. The enzyme also possesses a [3Fe–4S] iron–sulfur center in the same subunit as the molybdenum center, as well as a Rieske‐like [2Fe–2S] center in a separate, smaller, subunit. In addition to a detailed consideration of the enzyme's structure, its electrochemical and catalytic properties are discussed. Phylogenetic evidence is also discussed, suggesting that arsenite oxidase is an ancient enzyme arising before the diversification of the archaeal and eubacterial domains of life.
Manganese Catalase
Authors: Barynin Vladimir V , Whittaker James W 
Published: December 2011

AbstractManganese catalase (a.k.a. pseudocatalase, nonheme catalase) is an antioxidant defense metalloenzyme that is broadly distributed over prokaryotic life. While functionally related to heme catalases, manganese catalases have a distinct protein structure based on a four‐helix bundle architecture that is more closely related to the oxygen‐activating iron metalloproteins ferritin and ribonucleotide reductase. Manganese catalase contains a pair of manganese ions bound in the core of the four‐helix bundle in a solvent‐bridged binuclear cluster that serves as the catalytic active site for hydrogen peroxide disproportionation. Both metal ions are redoxactive, cycling between divalent and trivalent oxidation states during catalytic turnover.