SII-SWORD/CoKE huggingface dataset:
Cytochrome c oxidase, subunit I, copper-binding site (Cyt_c_Oxase_su1_BS)
Type: Binding_site

Cytochrome c oxidase (

) is a key enzyme in aerobic metabolism. Proton pumping haem-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-haem a3 (or haem o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (

), is directly involved in the coupling between dioxygen reduction and proton pumping .
Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes).

The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (CO I) is found in all haem-copper respiratory oxidases. The presence of a bimetallic centre (formed by a high-spin haem and copper B) as well as a low-spin haem, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members . In contrast to eukaryotes the respiratory chain of prokaryotes is branched to multiple terminal oxidases. The enzyme complexes vary in haem and copper composition, substrate type and substrate affinity. The different respiratory oxidases allow the cells to customize their respiratory systems according to a variety of environmental growth conditions .

This entry represents the copper-binding site of the cytochrome c oxidase subunit I. In particular, copper is ligated to three conserved histidine residues contained in this site .
Cytochrome c oxidase-like, subunit I domain (Cyt_c_oxase-like_su1_dom)
Type: Domain

Cytochrome c oxidase (

) is a key enzyme in aerobic metabolism. Proton pumping haem-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-haem a3 (or haem o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (

), is directly involved in the coupling between dioxygen reduction and proton pumping .
Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes).

The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (CO I) is found in all haem-copper respiratory oxidases. The presence of a bimetallic centre (formed by a high-spin haem and copper B) as well as a low-spin haem, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members . In contrast to eukaryotes the respiratory chain of prokaryotes is branched to multiple terminal oxidases. The enzyme complexes vary in haem and copper composition, substrate type and substrate affinity. The different respiratory oxidases allow the cells to customize their respiratory systems according to a variety of environmental growth conditions .

This entry represents a structural domain found in subunit I of cytochrome c oxidase as well as related proteins, including quinol oxidase.
Tyrosine-tRNA ligase, archaeal/eukaryotic-type (Tyr-tRNA-ligase_arc/euk-type)
Type: Family

Tyrosine-tRNA ligases (TyrRS; also known as Tyrosyl-tRNA synthetases) (

) are widely distributed, being found in archaea, bacteria and eukaryotes. TyrRS is a homodimer which attaches Tyr to the appropriate tRNA. TyrRS is a class I tRNA synthetases, so it aminoacylates the 2'-OH of the nucleotide at the 3' end of the tRNA. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the class I characteristic 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding. Studies have shown that the 'KMSKS' motif plays a role in the initial binding of tRNA(Tyr) to tyrosine-tRNA ligase .

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Two groups can be distinguished among tyrosyl-tRNA synthetases. One group contains bacterial and organellar eukaryotic examples. The other contains archaeal and cytosolic eukaryotic examples. This entry represents the archaeal and cytosolic eukaryotic tyrosyl-tRNA synthetases.
Photosystem I PsaG/PsaK domain, chloroplastic (PSI_PsaG/PsaK_dom)
Type: Homologous_superfamily

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. It is found in the chloroplasts of plants and cyanobacteria. PSI is composed of at least 14 different subunits, two of which are small hydrophobic proteins of about 7 to 9 Kd and evolutionary related, PsaG (also known as PSI-G) and PsaK (also known as PSI-K), both integral membrane proteins. Cyanobacteria contain only PsaK . While cyanobacterial PSI have phycobilisomes to harvest light, eukaryotic PSI have a membrane-imbedded peripheral antenna .

The domain represented by this entry consists of an α orthogonal bundle and it is found in photosystem I subunits PsaG and PsaK from chloroplasts.
Small protein B (SmpB)
Type: Homologous_superfamily

This entry represents SsrA-binding protein (aka small protein B or SmpB), which is a unique RNA-binding protein that is conserved throughout the bacterial kingdom and is an essential component of the SsrA quality-control system. Tight recognition of codon-anticodon pairings by the ribosome ensures the accuracy and fidelity of protein synthesis. In eubacteria, translational surveillance and ribosome rescue are performed by the 'tmRNA-SmpB' system (transfer messenger RNA-small protein B). SmpB binds specifically to the ssrA RNA (tmRNA) and is required for stable association of ssrA with ribosomes. SsrA RNA recognises ribosomes stalled on defective messages and acts to mediate the addition of a short peptide tag to the C terminus of the partially synthesised nascent polypeptide chain. Within a stalled ribosome, SmpB interacts with the three universally conserved bases G530, A1492 and A1493 that form the 30S subunit decoding centre, in which canonical codon-anticodon pairing occurs . The SsrA-tagged protein is then degraded by C-terminal-specific proteases. Formation of an SmpB-SsrA complex appears to be critical in mediating SsrA activity after aminoacylation with alanine but prior to the transpeptidation reaction that couples this alanine to the nascent chain . The SmpB protein has functional and structural similarities with initiation factor 1, and is proposed to be a functional mimic of the pairing between a codon and an anticodon.

The core of SmpB consists of an antiparallel β-barrel containing eight β-strands and three helices .
Large ribosomal subunit protein eL31 domain superfamily (Ribosomal_eL31_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain found in ribosomal proteins belonging to the eL31 family.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Antenna complex, beta subunit, conserved site (Antenna_beta_CS)
Type: Conserved_site

The antenna complexes of photosynthetic bacteria function as light-harvesting systems that absorb light and transfer the excitation energy to the reaction centres. The antenna complexes usually comprise 2 polypeptides (alpha- and beta-chains), 2-3 bacteriochlorophyll molecules and some carotenoids .
The alpha- and beta-chains are small proteins of 40-70 residues. Each has an N-terminal hydrophilic cytoplasmic domain, a single transmembrane (TM) region, and a small C-terminal hydrophilic periplasmic domain. In both chains, the TM domain houses a conserved His residue, presumed to be involved in binding the magnesium atom of a bacteriochlorophyll group. The beta-chains are characterised by a further histidine at the C-terminal extremity of the cytoplasmic domain, which is also thought to be involved in bacteriochlorophyll binding.

This entry represents a conserved site in the beta subunit that includes the histidine residues thought to be involved in bacteriochlorophyll binding.
Antenna complex, beta domain superfamily (Antenna_beta_dom_sf)
Type: Homologous_superfamily

The antenna complexes of photosynthetic bacteria function as light-harvesting systems that absorb light and transfer the excitation energy to the reaction centres. The antenna complexes usually comprise 2 polypeptides (alpha- and beta-chains), 2-3 bacteriochlorophyll molecules and some carotenoids .
The alpha- and beta-chains are small proteins of 40-70 residues. Each has an N-terminal hydrophilic cytoplasmic domain, a single transmembrane (TM) region, and a small C-terminal hydrophilic periplasmic domain. In both chains, the TM domain houses a conserved His residue, presumed to be involved in binding the magnesium atom of a bacteriochlorophyll group. The beta-chains are characterised by a further histidine at the C-terminal extremity of the cytoplasmic domain, which is also thought to be involved in bacteriochlorophyll binding.

This superfamily represents the structural domain of the beta subunit, encapsulating the N-terminal, TM and C-terminal domains.
Large ribosomal subunit protein eL39 domain superfamily (Ribosomal_eL39_dom_sf)
Type: Homologous_superfamily

This superfamily represents the structural domain found in ribosomal proteins belonging to the eL39 family, which includes eukaryotic and archaeal proteins.

A number of eukaryotic and archaebacterial large subunit ribosomal proteins can be grouped on the basis of sequence similarities. This entry represents the large ribosomal subunit protein eL39, of about 50 residues long, being the smallest protein of eukaryotic-type ribosomes. In mammals, eL39 has been described as the RNA-binding component of the large ribosomal subunit .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Recombination protein RecR (Rcmb_RecR)
Type: Homologous_superfamily

The bacterial protein RecR is an important regulator in the RecFOR homologous recombination pathway during DNA repair . It acts with RecF and RecO forming a complex that facilitates the loading of RecA onto ssDNA . RecR is a zinc metalloprotein consisting of a N-terminal helix-hairpin-helix (HhH) motif, a middle region containing a zinc finger motif and a Toprim domain, and a C-terminal domain comprising a divergent Walker B motif and a C-terminal helix .

This entry represents RecR's main structural domain, which consists of a N-terminal helix-hairpin-helix (HhH) motif, followed by a Cys4 zinc-finger motif, a Toprim domain and a Walker B motif .
Amidase signature domain (Amidase_dom)
Type: Domain

The amidase signature enzymes consist structurally of a core domain that is covered by α-helices .

Amidase signature (AS) enzymes are a large group of hydrolytic enzymes that contain a conserved stretch of approximately 130 amino acids known as the AS sequence. They are widespread, being found in both prokaryotes and eukaryotes. AS enzymes catalyse the hydrolysis of amide bonds (CO-NH2), although the family has diverged widely with regard to substrate specificity and function. Nonetheless, these enzymes maintain a core α/β/α structure, where the topologies of the N-and C-terminal halves are similar. AS enzymes characteristically have a highly conserved C-terminal region rich in serine and glycine residues, but devoid of aspartic acid and histidine residues, therefore they differ from classical serine hydrolases. These enzymes posses a unique, highly conserved Ser-Ser-Lys catalytic triad used for amide hydrolysis, although the catalytic mechanism for acyl-enzyme intermediate formation can differ between enzymes .

Examples of AS enzymes include:

Peptide amidase (Pam) , which catalyses the hydrolysis of the C-terminal amide bond of peptides.

Fatty acid amide hydrolases , which hydrolyse fatty acid amid substrates (e.g. cannabinoid anandamide and sleep-inducing oleamide), thereby controlling the level and duration of signalling induced by this diverse class of lipid transmitters.

Malonamidase E2 , which catalyses the hydrolysis of malonamate into malonate and ammonia, and which is involved in the transport of fixed nitrogen from bacteroids to plant cells in symbiotic nitrogen metabolism.

Subunit A of Glu-tRNA(Gln) amidotransferase ,a heterotrimeric enzyme that catalyses the formation of Gln-tRNA(Gln) by the transamidation of misacylated Glu-tRNA(Gln) via amidolysis of glutamine.
ATP synthase, F1 complex, gamma subunit conserved site (ATP_synth_F1_gsu_CS)
Type: Conserved_site

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

The ATPase F1 complex gamma subunit forms the central shaft that connects the F0 rotary motor to the F1 catalytic core. The gamma subunit functions as a rotary motor inside the cylinder formed by the α(3)β(3) subunits in the F1 complex . The most conserved region of the gamma subunit is its C terminus, which seems to be essential for assembly and catalysis.
Reovirus, outer capsid sigma-3 domain superfamily (Reovirus_capsid_sigma-3_dom_sf)
Type: Homologous_superfamily

Reoviruses are double-stranded RNA viruses that lack a membrane envelope. Their capsid is organised in two concentric icosahedral layers: an inner core and an outer capsid layer. The outer capsid is made up of the major proteins mu1 and sigma3, and the minor protein sigma1. The inner core structure is composed of the major core proteins lambda1 and sigma2, core spike protein lambda2, and minor core proteins lambda3 and mu2. The inner core encases the 10 segments of double-stranded RNA (dsRNA) which comprise the genome .

The structure of the Reovirus outer capsid protein sigma3 reveals a two-lobed structure organised around a long central helix. The smaller of the two lobes includes a CCHC zinc-binding site .
Peptide deformylase (Peptide_deformylase)
Type: Family

Peptide deformylase (PDF) is an essential metalloenzyme required for the removal of the formyl group at the N terminus of nascent polypeptide chains in eubacteria:

. The enzyme acts as a monomer and binds a single metal ion, catalysing the reaction:

N-formyl-L-methionine + H
2
O = formate + methionyl peptide

Catalytic efficiency strongly depends on the identity of the bound metal .

These enzymes utilize Fe(II) as the catalytic metal ion, which can be replaced with a nickel or cobalt ion with no loss of activity. There are two types of peptide deformylases, types I and II, which differ in structure only in the outer surface of the domain. Because these enzymes are essential only in prokaryotes (although eukaryotic gene sequences have been found), they are a target for a new class of antibacterial agents .

The structure of these enzymes is known . PDF, a zinc metalloenzyme from the mitochondrion, comprises an active core domain of 147 residues and a C-terminal tail of 21 residue. The 3D fold of the catalytic core has been determined by X-ray crystallography and NMR. Overall, the structure contains a series of anti-parallel β-strands that surround two perpendicular α-helices. The C-terminal helix contains the characteristic HEXXH motif of metalloenzymes, which is crucial for activity. The helical arrangement, and the way the histidine residues bind the zinc ion, is reminiscent of metalloproteases such as thermolysin or metzincins. However, the arrangement of secondary and tertiary structures of PDF, and the positioning of its third zinc ligand (a cysteine residue), are quite different. These discrepancies, together with notable biochemical differences, suggest that PDF constitutes a new class of zinc-metalloenzymes .
Urocanase conserved site (Urocanase_CS)
Type: Conserved_site

This entry represents a conserved site found in the C-terminal part of Urocanase. It is found also in S-methyl thiourocanate hydratase which cannot use urocanate or thiourocanate as substrate and catalyses the conversion of S-methyl thiourocanate, to S-methyl-thiohydantoin-5-propanoate .

Urocanase (also known as imidazolonepropionate hydrolase or urocanate hydratase) is the enzyme that catalyses the second step in the degradation of histidine, the hydration of urocanate into imidazolonepropionate:

urocanate + H
2
O = 4,5-dihydro-4-oxo-5-imidazolepropanoate

Urocanase is found in some bacteria (gene hutU) , in the liver of many vertebrates, and has also been found in the plant Trifolium repens (white clover). Urocanase is a protein of about 60 Kd, it binds tightly to NAD
+
and uses it as an electrophil cofactor. A conserved cysteine has been found to be important for the catalytic mechanism and could be involved in the binding of the NAD
+
.