SII-SWORD/CoKE huggingface dataset:
Vibrio cholerae toxin co-regulated pilus biosynthesis F, C-terminal (TcpF_C)
Type: Homologous_superfamily

Vibrio cholerae relies on two main virulence factors, the toxin co-regulated pilus (TCP) and cholera toxin, to cause the gastrointestinal disease cholera. TCP is a type IV pilus that mediates bacterial auto-agglutination and colonisation of the intestine. TCP is encoded by the tcp operon, which also encodes TcpF (toxin co-regulated pilus biosynthesis protein F). TcpF is a soluble secreted protein that is critical for V. cholerae colonisation, although its exact role in this process has yet to be determined. This protein is comprised by N- and C-terminal domains joined by a linker, suggesting that the cleft between the domains is used to bind to a substrate .

This entry represents the C-terminal domain TcpF.
Esp1, core domain (Esp1_core)
Type: Homologous_superfamily

Exocrine gland-secreting peptide Esp1 is produced by the rodent male extraorbital lacrimal gland to be secreted into the tear fluid. Other mice, including females, detect these peptides through receptors in the vomeronasal organ, and the receptors report information on mouse-strain, sex and species . The peptides are short, all carrying an N-terminal signal peptide to indicate they are for secretion which accounts for much of the common conservation. Structurally, Esp1 consists of three helices with an overall helical fold stabilised by an intramolecular disulfide bridge.

This superfamily represents the Esp1 core domain.
Sec1-like, domain 3a (Sec-1-like_dom3a)
Type: Homologous_superfamily

This superfamily represents the N-terminal region of domain 3 (called domain 3a) found in Sec1 and related proteins.

Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis . They regulate vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought to prevent SNARE complex formation, a protein complex required for membrane fusion. Whereas Sec1 molecules are essential for neurotransmitter release and other secretory events, their interaction with syntaxin molecules seems to represent a negative regulatory step in secretion .

The nSec1 polypeptide chain can be divided into three domains. The first domain, consists of a five-stranded parallel β-sheet flanked by five α-helices. The second domain, like the first one, has an α-β-α fold, however the β-sheet of domain 2 features five parallel strands with an additional antiparallel strand on one edge. The third domain is a large insertion between the third and fourth parallel strands of domain 2, and can be subdivided in two .

Members of the Sec1 family include Sec1, Sly1, Slp1/Vps33, Vps45/Stt10 (yeast), Unc-18 (nematode), Munc-18b/muSec1, Munc-18c (mouse), Rop (Drosophila), Munc-18/n-Sec1/rbSec1A and rbSec1B (rat) .
Reverse transcriptase/Diguanylate cyclase domain (Rev_trsase/Diguanyl_cyclase)
Type: Homologous_superfamily

This superfamily comprises domains found in several proteins such as reverse transcriptase , DNA polymerase IV and several nucleotide cyclases, such as the nucleotide-binding GGDEF domain.

The representative domains have DNA-directed DNA polymerase, RNA-directed RNA polymerase and diguanylate cyclase activities, and are involved in viral replication, signal transduction, nucleotide binding, and hydrolysis of cyclic diguanylate.
ATPase, nucleotide binding domain (ATPase_NBD)
Type: Homologous_superfamily

This superfamily comprises domains found in several ATPases, including actin, Hsp70, BadF/BadG/BcrA/BcrD, various kinases, DnaK, ROK, PilM, and Fumble. Members of this superfamily have two lobes, one with nucleotide binding activity, and a second one with substrate binding activity. The lobes can be structurally divided into 4 subdomains - 1A, 1B, 2A, 2B (or 1, 2, 3, 4). The ATP binding site in these ATPases is well conserved, and is located at the junction of the two lobes, in a deep cleft. This superfamily entry represents the nucleotide binding domain (NBD) or the first lobe (subdomains 1A and 1B), which exhibits ATPase activity.
CDP-alcohol phosphatidyltransferase, transmembrane domain (CDP-OH_PTrfase_TM_dom)
Type: Homologous_superfamily

The CDP-alcohol phosphotransferase (CDP-AP) family of integral membrane enzymes catalyses the transfer of a substituted phosphate group from a CDP-linked donor to an alcohol acceptor. This is an essential reaction for phospholipid biosynthesis across all kingdoms of life, and it is catalysed solely by CDP-APs . This entry represents the transmembrane (TM) domain of CDP-alcohol phosphotransferase which is made up of 7 α helices.
Branched-chain-amino-acid aminotransferase-like, N-terminal (BCAT-like_N)
Type: Homologous_superfamily

This entry represents the N-terminal small domain of BCATs .

Branched-chain aminotransferase (BCAT) catalyses the transamination of the branched-chain amino acids leucine, isoleucine and valine to their respective alpha-keto acids, alpha-ketoisocaproate, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. The enzyme requires pyridoxal 5'-phosphate (PLP) as a cofactor to catalyse the reaction. It has been found that mammals have two forms of the enzyme - mitochondrial and cytosolic forms, while bacteria contain only one form of the enzyme . BCATs belong to the class 4 type aminotransferases and are widely distributed in many species . Structurally, BCAT comprises two domains, the small domain consists of 7 β-strands and 3 α-helices, the large domain contains 6 β-strands and 3 α-helices .

Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies.
Branched-chain-amino-acid aminotransferase-like, C-terminal (BCAT-like_C)
Type: Homologous_superfamily

This entry represents the C-terminal large domain of BCATs.

Branched-chain aminotransferase (BCAT) catalyses the transamination of the branched-chain amino acids leucine, isoleucine and valine to their respective alpha-keto acids, alpha-ketoisocaproate, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate. The enzyme requires pyridoxal 5'-phosphate (PLP) as a cofactor to catalyse the reaction. It has been found that mammals have two forms of the enzyme - mitochondrial and cytosolic forms, while bacteria contain only one form of the enzyme . BCATs belong to the class 4 type aminotransferases and are widely distributed in many species . Structurally, BCAT comprises two domains, the small domain consists of 7 β-strands and 3 α-helices, the large domain contains 6 β-strands and 3 α-helices .

Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies.
GTP cyclohydrolase I, C-terminal/NADPH-dependent 7-cyano-7-deazaguanine reductase (GTP-CH-I_C/QueF)
Type: Homologous_superfamily

GTP cyclohydrolase I (

) catalyses the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP . This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. The comparison of the sequence of the enzyme from bacterial and eukaryotic sources shows that the structure of this enzyme has been extremely well conserved throughout evolution .

The QueF (NADPH-dependent 7-cyano-7-deazaguanine reductase) monomer is made up of two ferredoxin-like domains aligned together with their β-sheets that have additional embellishments. QueF catalyses the reduction of the nitrile group of 7-cyano-7-deazaguanine to 7-aminomethyl-7-deazaguanine . QueF reduces a nitrile bond to a primary amine. The two monomer units together create suitable substrate-binding pockets.

This superfamily entry consists of the C-terminal domain found in GTP cyclohydrolases I (GTP-CH-I), which has been well conserved throughout evolution across bacterial and eukaryotic species. The C-terminal domain contains the regions relevant for oligomerisation and enzyme catalysis. The structure of the C-terminal domain of GTP-CH-I is topologically identical to PTPS (6-pyruvoyl tetrahydropterin synthase), despite the lack of sequence homology with PTPS . The superfamily also includes a domain from NADPH-dependent 7-cyano-7-deazaguanine reductase (QueF). This domain is composed of a three-stranded β-sheet and two α-helices.
GTP cyclohydrolase I, N-terminal domain (GTP-CH-I_N)
Type: Homologous_superfamily

GTP cyclohydrolase I (

) catalyses the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP . This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. The comparison of the sequence of the enzyme from bacterial and eukaryotic sources shows that the structure of this enzyme has been extremely well conserved throughout evolution .

This superfamily entry consists of the N-terminal domain found in GTP cyclohydrolases I (GTP-CH-I), which has been well conserved throughout evolution across bacterial and eukaryotic species. The GTP-CH-I monomer folds into an α β structure with a predominantly helical N-terminal part .
Ferric-uptake regulator, C-terminal domain (Fur_C)
Type: Homologous_superfamily

The ferric uptake regulator (Fur) family includes metal ion uptake regulator proteins, which are responsible for controlling the intracellular concentration of iron in many bacteria. Some members sense metal ions other than Fe2. For example, the zinc uptake regulator (Zur) responds to Zn2 , the manganese uptake regulator (Mur) responds to Mn2 , and the nickel uptake regulator (Nur) responds to Ni2 . Fur family proteins contain an N-terminal winged-helix DNA-binding domain followed by a C-terminal dimerisation domain.

This entry represents the dimerisation domain in which three antiparallel β-strands are covering a long α-helix .
B30.2/SPRY domain superfamily (B30.2/SPRY_sf)
Type: Homologous_superfamily

This superfamily also matches diverse E3 ubiquitin-protein ligases. This protein is involved in the apoptosis process .

The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region , whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors . B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction .
The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains . The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) . The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short β-helices at the N terminus. The β-sandwich of the B30.2/SPRY domain consists of two layers of β-sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the β-strands are in antiparallel arrangement . The 5th β-strand corresponding to WEVE motif . Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other .
Gamma-glutamyltranspeptidase, small subunit, C-terminal domain (GGT_ssub_C)
Type: Homologous_superfamily

This entry represents the C-terminal domain in the small subunit of GGT.

Gamma-glutamyltranspeptidase (

) (GGT) is a heterodimeric enzyme that is generated from the precursor protein through post-translational processing, and catalyses the hydrolysis of gamma-glutamyl bonds in gamma-glutamyl compounds. GGT has a stacked α-β-β-α fold comprising the large and small subunits, similar to the folds seen in members of the N-terminal nucleophile hydrolase superfamily .
Gamma-glutamyltranspeptidase, large subunit (GGT_lsub)
Type: Homologous_superfamily

This entry represents the large subunit found in GGT.

Gamma-glutamyltranspeptidase (

) (GGT) is a heterodimeric enzyme that is generated from the precursor protein through post-translational processing, and catalyses the hydrolysis of gamma-glutamyl bonds in gamma-glutamyl compounds. GGT has a stacked α-β-β-α fold comprising the large and small subunits, similar to the folds seen in members of the N-terminal nucleophile hydrolase superfamily .
Small ribosomal subunit protein uS14 superfamily (Ribosomal_uS14_sf)
Type: Homologous_superfamily

This superfamily entry represents the ribosomal protein uS14 found in the small (30S) subunit of the bacterial, algal and plant cytoplasmic ribosome. This entry also includes homologues such as cyanelle uS14, archaebacteria Methanococcus vannielii uS14, as well as yeast YS29A/B, and mammalian S29, but it does not include mitochondrial members.

In E. coli, uS14 is known to be required for the assembly of 30S particles and may also be responsible for determining the conformation of 16S rRNA at the A site. S29 has zinc-finger-like motifs .

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 .
PapC-like, C-terminal domain superfamily (PapC-like_C_sf)
Type: Homologous_superfamily

The PapC C-terminal domain is a structural domain found at the C terminus of the E. coli protein PapC. In E.coli pili are assembled using the chaperone usher system composed of the chaperone PapD and the usher PapC. This superfamily represents the C-terminal domain from PapC and its homologues. This domain has a β-sandwich structure similar to the plug domain of PapC .
Malate/L-sulfolactate/L-lactate dehydrogenase-like, NADPH binding domain (Mal/L-sulf/L-lact_DH-like_NADP)
Type: Homologous_superfamily

The malate dehydrogenase (MDH) of some extremophiles is more similar to the L-lactate dehydrogenases (L-LDH;

) from various sources than to other MDHs . The archaebacterial MDH deviates from the eubacterial and eukaryotic enzymes having a low selectivity for the coenzyme (NAD(H) or NADP(H)) and catalysing the reduction of oxaloacetate to malate more efficiently than the reverse reaction . It has been suggested that this class of dinucleotide cofactor-dependent dehydrogenases do not contain a Rossman-fold motif, as it was prior believed to be the case .

The enzyme is a dimer, where each subunit consists of three domains: domain I, domain II (NADPH binding domain), and domain III. Domain I contains N- and C-terminal regions and consists of the four-helix bundle . The NADPH binding domain is formed of a seven-stranded antiparallel β-sheet fold .

This superfamily consists of the NADPH binding domain found in bacterial and archaeal enzymes with malate, L-lactate, L-sulpholactate dehydrogenase activities, and related proteins.
Malate/L-sulfolactate/L-lactate dehydrogenase-like, alpha-helical domain (Mal/L-sulf/L-lact_DH-like_ah)
Type: Homologous_superfamily

The malate dehydrogenase (MDH) of some extremophiles is more similar to the L-lactate dehydrogenases (L-LDH;

) from various sources than to other MDHs . The archaebacterial MDH deviates from the eubacterial and eukaryotic enzymes having a low selectivity for the coenzyme (NAD(H) or NADP(H)) and catalysing the reduction of oxaloacetate to malate more efficiently than the reverse reaction . It has been suggested that this class of dinucleotide cofactor-dependent dehydrogenases do not contain a Rossman-fold motif, as it was prior believed to be the case .

The enzyme is a dimer, where each subunit consists of three domains: domain I, domain II (NADPH binding domain), and domain III. Domain I contains N- and C-terminal regions and consists of the four-helix bundle . The NADPH binding domain is formed of a seven-stranded antiparallel β-sheet fold .

This superfamily represents an α-helical domain found in bacterial and archaeal enzymes with malate, L-lactate, L-sulpholactate dehydrogenase activities, and related proteins. This domain has a four-helix barrel topology which forms an antiparallel pack, and is different from the typical four-helix bundle.
Zinc finger, ZZ-type superfamily (Znf_ZZ_sf)
Type: Homologous_superfamily

This entry represents the ZZ domain, which belongs to the family of 'cross-brace' zinc finger proteins with interleaved zinc binding sites. These zinc fingers are thought to be involved in protein-protein interactions .

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
Penicillin amidase type, N-terminal domain, B-knob (Penicillin_amidase_N_B-knob)
Type: Homologous_superfamily

Penicillin amidase or penicillin acylase catalyses the hydrolysis of benzylpenicillin to phenylacetic acid and 6-aminopenicillanic acid (6-APA) a key intermediate in the the synthesis of penicillins .

This superfamily represents enzymes that share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing. They are part of the Ntn (N-terminal nucleophile) hydrolases family .

Cephalosporin acylase from Pseudomonas diminuta (known as CAD) consists of an alpha-subunit with 169 residues and a beta-subunit with 520 residues. The enzyme is described as a bowl-shaped molecule with two knobs attached to the bowl, facing each other. The A-knob contains mostly α-helices, whereas the B-knob contains mostly β-sheets . The B-knob region is made up of seven β-strands which form a distorted β-barrel-like domain. This superfamily entry comprises structural domains similar to the β-sheet B-knob region described in CAD.
Penicillin amidase type, A-knob (Penicillin_amidase_A-knob)
Type: Homologous_superfamily

Penicillin amidase or penicillin acylase catalyses the hydrolysis of benzylpenicillin to phenylacetic acid and 6-aminopenicillanic acid (6-APA) a key intermediate in the the synthesis of penicillins .

This superfamily represents enzymes that share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing. They are part of the Ntn (N-terminal nucleophile) hydrolases family .

Cephalosporin acylase from Pseudomonas diminuta (also known as CAD) consists of an alpha-subunit with 169 residues and a beta-subunit with 520 residues. The enzyme is described as a bowl-shaped molecule with two knobs attached to the bowl, facing each other. The A-knob contains mostly α-helices, whereas the B-knob contains mostly β-sheets . The A-knob is made up of five helices and a short β-strand. This superfamily entry comprises structural domains similar to the α-helical A-knob region described in CAD.
CDP-glycerol glycerophosphotransferase, C-terminal domain (TagF_C)
Type: Homologous_superfamily

Wall-associated teichoic acids are a heterogeneous class of phosphate-rich polymers that are covalently linked to the cell wall peptidoglycan of Gram-positive bacteria. They consist of a main chain of phosphodiester-linked polyols and/or sugar moieties attached to peptidoglycan via a linkage unit. CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase TagF is responsible for the polymerisation of the main chain of the teichoic acid by sequential transfer of glycerol-phosphate units from CDP-glycerol to the linkage unit lipid . The TagF-like family of enzymes has been shown to be responsible for wall teichoic acid priming and polymerization events .

This entry represents the C-terminal domain of TagF which exhibits a Rossmann-fold.