SII-SWORD/CoKE huggingface dataset:
Homoserine/serine acetyltransferase MetX-like (HAT_MetX-like)
Type: Family

Homoserine acetyltransferase (homoserine transacetylase) catalyses the first step unique to methionine biosynthesis, converting L-homoserine to O-acetyl-L-homoserine using acetyl-CoA as an acetyl group donor . This enzyme regulates homoserine in a number of biosynthetic pathways, making it vital to cell growth and viability. The biosynthesis of methionine in particular has been shown to be susceptible to small-molecule inhibition in fungi and is consequently a good candidate for antifungal agents .

This family also includes serine O-acetyltransferases, involved in cysteine biosynthesis , and deacetylcephalosporin C acetyltransferase CefG, closely related to homoserine O-acetyltransferase and involved in cephalosporin biosynthesis .

Acetyltransferase efuC from the fungus Hormonema carpetanum also belongs to this group. It plays a role in the biosynthesis of enfumafungin, a glycosylated fernene-type triterpenoid with potent antifungal activity .
Urease (Urease)
Type: Family

Urease (urea amidohydrolase,

) catalyses the hydrolysis of urea to form ammonia and carbamate. The subunit composition of urease from different sources varies , but each holoenzyme consists of four structural domains : three structural domains and a nickel-binding catalytic domain common to amidohydrolases . Urease is unique among nickel metalloenzymes in that it catalyses a hydrolysis rather than a redox reaction. In Klebsiella aerogenes, the domains are found in an alpha subunit (with the C-terminal two-thirds representing the catalytic domain and the N-terminal one-third representing one of the structural domains); a beta subunit, and a gamma subunit. In Helicobacter pylori, the gamma and beta domains are fused and called the alpha subunit. The catalytic subunit (called beta or B) has the same organisation as the K. aerogenes alpha subunit. Jack bean (Canavalia ensiformis) urease has a fused gamma-beta-alpha organisation.

This group represents the gamma-beta-alpha type.
Urease, gamma-beta subunit (Urease_gamma-beta_su)
Type: Family

This entry represents the fused gamma-beta organisation typified by the H. pylori alpha subunit.

Urease (urea amidohydrolase,

) is a nickel-dependent metalloenzyme that catalyses the hydrolysis of urea to form ammonia and carbon dioxide. Nickel-dependent ureases are found in bacteria, archaea, fungi and plants. Their primary role is to allow the use of external and internally-generated urea as a nitrogen source. The enzyme consists of three subunits, alpha, beta and gamma, which can exist as separate proteins or can be fused on a single protein chain. The α-β-γ heterotrimer forms multimers, mainly trimers. The subunit composition of urease from different sources varies , but each holoenzyme consists of four domains : three structural domains and a nickel-binding catalytic domain common to amidohydrolases .

In Klebsiella aerogenes, urease exists as an alpha, beta and gamma subunit, with the alpha subunit possessing the catalytic domain. In Helicobacter pylori, the gamma and beta subunits are fused and called the alpha subunit, while the catalytic subunit is called the beta subunit. In Canavalia ensiformis, urease has a fused gamma-beta-alpha organisation.
Coenzyme F420:L-glutamate ligase (F420-0_g-glutamyl_ligase)
Type: Family

FbiB catalyses the GTP-dependent successive addition of multiple gamma-linked L-glutamates to the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) to form polyglutamated F420 derivatives . It is also involved in the FMNH2-dependent reduction of dehydro-F420-0 to form F420-0 .
Mini-ribonuclease 3 family (Mini3_fam)
Type: Family

This family consists of the mini-ribonuclease 3 (mini-3) and mini-3 like proteins. Mini-3 is involved in correct processing of both the 5' and 3' ends of 23S rRNA precursor. It processes 30S rRNA precursor transcript even in absence of ribonuclease 3 (Rnc); Rnc processes 30S rRNA into smaller rRNA precursors . Mini-3 like proteins in this entry strongly resemble the Mini-3 enzyme, but are missing a highly conserved, possibly catalytically important site at position 72.
Uncharacterised conserved protein UCP006173 (UCP006173)
Type: Family

There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. They contain multiple conserved cysteine residues, which may indicate metal binding.
tRNA nucleotidyltransferase, archaea (CCA-adding_arc)
Type: Family

All mature tRNAs contain a terminal CCA sequence essential for function . CCA-adding enzyme ensures that each tRNA contains a terminal CCA, either by de novo addition or by repair of a damaged end . CCA-adding enzyme of this group is a class I nucleotidyltransferase unrelated, except at the active site, to class II CCA-adding enzymes (

) ). Interestingly, despite the fact that class I CCA-adding enzyme combines tRNA cytidylyltransferase (

) and tRNA adenylyltransferase (

) activities, it possesses only one active site per monomer . However, stoichiometric analysis shows formation of a tetramer upon binding of only two tRNA molecules, raising the possibility that two active sites, each responsible for a different nucleotide, form adjacent to each substrate molecule.
Probable chaperone CsaA (CsaA)
Type: Family

This entry describes CsaA, an export-related chaperone that interacts with the Sec system, and related proteins from a number of other bacteria and archaea . The crystal structure is known for the homodimer from Thermus thermophilus .
Chorismate mutase, AroQ class, eukaryotic type (Chorismate_mutase_AroQ_euk)
Type: Family

This entry represents chorismate mutase from eukaryotes.

Chorismate mutase (CM) is a regulatory enzyme (

) required for biosynthesis of the aromatic amino acids phenylalanine and tyrosine. CM catalyzes the Claisen rearrangement of chorismate to prephenate, which can subsequently be converted to precursors of either L-Phe or L-Tyr. In bifunctional enzymes the CM domain can be fused to a prephenate dehydratase (P-protein for Phe biosynthesis), to a prephenate dehydrogenase (T-protein, for Tyr biosynthesis), or to 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase (

). Besides these prokaryotic bifunctional enzymes, monofunctional CMs occur in prokaryotes as well as in fungi, plants and nematode worms .

The type I or AroH class of CM is represented by Bacillus subtilis aroH, a monofunctional, nonallosteric, homotrimeric enzyme characterised by its pseudo-α/β-barrel 3D structure. Each monomer folds into a 5-stranded mixed β-sheet packed against an α-helix and a 3-10 helix. The core is formed by a closed barrel of mixed β-sheets surrounded by helices. The interfaces between adjacent subunits form three equivalent clefts that harbor the active sites .

The type II or AroQ class of CM has a completely different all-helical 3D structure, represented by the CM domain of the bifunctional Escherichia coli P-protein. This type is named after the Enterobacter agglomerans monofunctional CM encoded by the aroQ gene . All CM domains from bifunctional enzymes as well as most monofunctional CMs belong to this class, including archaeal CM.

Eukaryotic CM from plants and fungi form a separate subclass of AroQ, represented by the Baker's yeast allosteric CM . These enzymes show only partial sequence similarity to the prokaryotic CMs due to insertions of regulatory domains, but the helix-bundle topology and catalytic residues are conserved and the 3D structure of the E. coli CM dimer resembles a yeast CM monomer . The E. coli P-protein CM domain consists of 3 helices and lacks allosteric regulation. The yeast CM has evolved by gene duplication and dimerisation, and each monomer has 12 helices. Yeast CM is allosterically activated by Trp and inhibited by Tyr .
Chorismate mutase, periplasmic (Chorismate_mutase_periplasmic)
Type: Family

Chorismate mutase (CM;

) catalyses the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. Members of this family contain a chorismate mutase domain of the AroQ class (prokaryotic type) that has an all-helical structure.

The three types of CM are AroQ class, prokaryotic type; AroQ class, eukaryotic type; and AroH class. They fall into two structural folds (AroQ class and AroH class) which are completely unrelated . The two types of the AroQ structural class (the Escherichia coli CM dimer and the yeast CM monomer) can be structurally superimposed, and the topology of the four-helix bundle forming the active site is conserved .

Periplasmic chorismate mutases form a subclass of the AroQ class, and are twice the size of cytoplasmic AroQ proteins due to a carboxy-terminal domain of unknown function . This C-terminal domain is so far unique to members of this group.

For additional information please see .
Salicylate biosynthesis protein PchB (Isochorismate_pyruvate-lyase)
Type: Family

Isochorismate pyruvate-lyase (IPL; PchB) catalyses the second reaction in the pyochelin biosynthetic pathway of Pseudomonas aeruginosa, conversion of isochorismate to salicylate plus pyruvate (following the initial PchA-dependent conversion of chorismate to isochorismate) . This enzyme can also carry out the chorismate mutase (CM) reaction, but with a low catalytic efficiency. It is unlikely that PchB plays a significant role in aromatic amino acid biosynthesis. This enzyme is a stand-alone version of a chorismate mutase domain of the AroQ class.

The three types of CM are AroQ class, prokaryotic type; AroQ class, eukaryotic type; and AroH class. They fall into two structural folds (AroQ class and AroH class) which are completely unrelated . The two types of the AroQ structural class (the Escherichia coli CM dimer and the yeast CM monomer) can be structurally superimposed, and the topology of the four-helix bundle forming the active site is conserved .

The PchB-type of chorismate mutase domain, while sharing conserved residues and the predicted secondary structure with the other subgroups of the AroQ class (prokaryotic type), has isochorismate pyruvate-lyase (IPL) as a primary catalytic activity. PchB can still use the same active site either for the IPL or for the CM reaction. It has been suggested that PchB was derived from an AroQ-class CM by a gene duplication event followed by selection for efficient IPL function in the course of the evolution of the pyochelin siderophore pathway, with only residual CM activity remaining. It can be further speculated that contemporary CMs may already possess (weak) IPL activity .

For additional information please see .
Bifunctional P-protein, chorismate mutase/prephenate dehydratase (Chor_mutase/pphenate_deHydtase)
Type: Family

The bifunctional P-protein, which plays a central role in phenylalanine biosynthesis, contains two catalytic domains (chorismate mutase and prephenate dehydratase) and a regulatory domain (ACT). It is part of the shikimate pathway, which is present only in bacteria, fungi, and plants.

Chorismate mutase (CM;

) catalyses the rearrangement of chorismate to prephenate, the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). The chorismate mutase domain of this protein belongs to the AroQ class (prokaryotic type) and has an all-helical structure. There are stand-alone versions of this domain, as well as fusions to other catalytic domains (such as prephenate dehydrogenase or DAHP synthase), or to regulatory domains.

Prephenate dehydratase (PDT;

) converts prephenate to phenylpyruvate. In the Escherichia coli P-protein, the ACT domain has been shown to be essential for phenylalanine-mediated feedback inhibition and ligand binding . It is a ligand-binding regulatory domain found primarily in enzymes and regulators of amino acid and purine metabolism .
Chorismate mutase, AroH class (Chorismate_mutase_AroH)
Type: Family

Chorismate mutase (CM) (

) catalyses the conversion of chorismate to prephenate in the shikimate pathway of tyrosine and phenylalanine biosynthesis in bacteria, fungi and plants .

The three types of CM are AroH class, AroQ class, prokaryotic type and AroQ class, eukaryotic type. Structurally CMs can be divided into two main groups: type I (AroH class) and type II (AroQ class). Type I (AroH) CMs include CMs characterised by a trimeric pseudo α/β barrel structure . The two types of the AroQ structural class (the Escherichia coli CM dimer and the yeast CM monomer) can be structurally superimposed, and the topology of the four-helix bundle forming the active site is conserved . CMs can be monofunctional or bifunctional (generally fused to another shikimate pathway member). Despite the structural differences, all CMs perform the same basic reaction .

This entry represents chorismate mutases of the AroH class predominantly from Terrabacteria.
Bifunctional chorismate mutase/prephenate dehydrogenase T-protein (Chor_mut/prephenate_DH_T)
Type: Family

The bifunctional T-protein (TyrA), which plays a central role in tyrosine biosynthesis, contains two catalytic domains (chorismate mutase and prephenate dehydrogenase). It is part of the shikimate pathway, which is present only in bacteria, fungi and plants. It is feedback inhibited by tyrosine. Chorismate mutase (CM;

) catalyses the rearrangement of chorismate to prephenate, the reaction at the branch point of the biosynthetic pathway leading to the three aromatic amino acids, phenylalanine, tryptophan and tyrosine (chorismic acid is the last common intermediate, and CM leads to the L-phenylalanine/L-tyrosine branch). The chorismate mutase domain of this protein belongs to the AroQ class (prokaryotic type), and has an all-helical structure. There are stand-alone versions of this domain, as well as fusions to other catalytic domains (such as prephenate dehydratase or DAHP synthase), or to regulatory domains. Prephenate dehydrogenase (PDH;

) catalyses the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate.

For additional information please see .
Uncharacterised protein family UPF0231 (UPF0231)
Type: Family

This family of uncharacterised proteins contains UPF0231 protein YacL from Escherichia coli and other proteins mainly found in Gammaproteobacteria.
P-type ATPase, A domain superfamily (ATPase_P-typ_transduc_dom_A_sf)
Type: Homologous_superfamily

This superfamily represents the actuator (A) domain, and some transmembrane helices found in P-type ATPases . It contains the TGES-loop which is essential for the metal ion binding which results in tight association between the A and P (phosphorylation) domains . It does not contain the phosphorylation site. It is thought that the large movement of the actuator domain, which is transmitted to the transmembrane helices, is essential to the long distance coupling between formation/decomposition of the acyl phosphate in the cytoplasmic P-domain and the changes in the ion-binding sites buried deep in the membranous region . This domain has a modulatory effect on the phosphoenzyme processing steps through its nucleotide binding .

P-ATPases (also known as E1-E2 ATPases) (

) are found in bacteria and in a number of eukaryotic plasma membranes and organelles . P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H
+
, Na
+
, K
+
, Mg
2+
, Ca
2+
, Ag
+
and Ag
2+
, Zn
2+
, Co
2+
, Pb
2+
, Ni
2+
, Cd
2+
, Cu
+
and Cu
2+
. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.

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.
Chromo shadow domain (Chromo_shadow_dom)
Type: Domain

Chromo shadow domain is distantly related to chromo domain. It is always found in association with a chromo domain.
Peptidase S15, X-Pro dipeptidyl-peptidase (Pept_S15_Xpro)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This family of sequences are serine peptidases belonging to MEROPS peptidase family S15 (clan SC) . The type example is X-Pro dipeptidyl-peptidase of Lactococcus lactis.

These proteins, which have similar specificity to mammalian dipeptidyl-peptidase IV, cleave Xaa-Pro releasing N-terminal dipeptides. The penultimate residue must be proline. In L. lactis the proteins exist as cytoplasmic homodimers .
Marvel domain (Marvel)
Type: Domain

This entry represents the ~130-residue MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. The MARVEL domain is a module with a four transmembrane-helix architecture that has been identified in proteins of the myelin and lymphocyte (MAL), physins, gyrins and occludin families. All described MARVEL domain-containing proteins are consistent with the M-shaped topology: four transmembrane-helix region architecture with cytoplasmic N- and C-terminal regions. Their function could be related to cholesterol-rich membrane apposition events in a variety of cellular processes, such as biogenesis of vesicular transport carriers or tight junction regulation .
Flavodoxin/nitric oxide synthase (Flavodoxin/NO_synth)
Type: Domain

This domain is found in a number of proteins including flavodoxin and nitric-oxide synthase. Flavodoxins are electron-transfer proteins that function in various electron transport systems. They bind one FMN molecule, which serves as a redox-active prosthetic group and are functionally interchangeable with ferredoxins. They have been isolated from prokaryotes, cyanobacteria, and some eukaryotic algae. Nitric oxide synthase (

) produces nitric oxide from L-arginine and NADPH. Nitric oxide acts as a messenger molecule in the body.

The flavodoxin-like domain is an around 170-residue domain with a flavin mononucleotide (FMN)-binding site. It is involved in electron transfer
reactions .

Structure analyses of several flavodoxin-like domains have shown that it is a wound α-β-α fold with a central 5-stranded parallel hydrophobic β-sheet flanked on either side by amphipathic α-helices . The FMN is positioned at the tip of the C-terminal side of the β-sheet . The fold correlates with a highly conserved, repetitive sequence pattern in which hydrophobic residues cluster in β-strands and have a 3-4-residue periodicity in α-helices .
Peptidase S1B (Peptidase_S1B)
Type: Family

This group of serine peptidases belong to the MEROPS peptidase family S1, subfamily S1B (clan PA(S)). A type example is glutamyl endopeptidase I from Staphylococcus aureus.

Other members include S. aureus V8 protease, which preferentially cleaves peptide bonds C-terminal to Asp and Glu residues; Bacillus licheniformis glutamate-specific endopeptidase , which also cleaves on the C-terminal side of acidic residues, but with strong preference for glutamate; Bacillus subtilis extracellular 'metalloprotease' ; and S. aureus exfoliative (or epidermolytic) toxins A and B, which cause impetigous diseases (also known as Staphylococcal scalded skin syndrome).

In a number of prokaryotic proteases the catalytic activity is provided by a charge relay system analogous to that of the trypsin family of serine proteases, but which probably evolved by independent convergent evolution . The sequences around the catalytic residues (Asp, Ser and His) are completely different from those of the corresponding residues in trypsin serine proteases, although these proteins also contain the serine protease trypsin family signatures.
Peptidase M19 (Pept_M19)
Type: Family

This group of peptidases belong to the MEROPS peptidase family M19 (membrane dipeptidase family, clan MJ). The protein fold of the peptidase domain for members of this family resembles that of Klebsiella urease, the type example for clan MJ .

Renal dipeptidase (

), also known as microsomal dipeptidase or membrane-bound dipeptidase, is a zinc-dependent metalloenzyme that hydrolyses a wide range of dipeptides. It is involved in renal metabolism of glutathione and its conjugates. It is a homodimeric disulphide-linked glycoprotein attached to the renal brush border microvilli membrane by a GPI-anchor. A glutamate residue has recently been shown to be important for the catalytic activity of renal dipeptidase. Renal dipeptidase seems to be evolutionary related to hypothetical proteins in the PQQ biosynthesis operons of Acinetobacter calcoaceticus and Klebsiella pneumoniae .
Transglycosylase SLT domain 1 (Transglycosylase_SLT_dom_1)
Type: Domain

This domain is found mainly in proteins from phages and type II, type III and type IV secretion systems .

Bacterial lytic transglycosylases degrade murein via cleavage of the beta-1,4-glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine, with the concomitant formation of a 1,6-anhydrobond in the muramic acid residue. There are both soluble (Slt enzymes) and membrane-bound (Mlt enzymes) lytic transglycosylases that differ in size, sequence, activity, specificity and location. The multi-domain structure of the 70 Kd soluble lytic transglycosylase Slt70 is known . Slt70 has 3 distinct domains, each rich in α helices: an N-terminal superhelical U-shaped domain, a superhelical linker domain (L-domain,

), and a C-terminal catalytic domain (

). Both the U-and L-domain share a similar superhelical structure. These two domains are connected, and together form a closed ring with a large central hole; the catalytic domain is packed on top of, and interacts with, this ring. The catalytic domain has a lysosome-like fold.
FMN-dependent alpha-hydroxy acid dehydrogenase, active site (FMN_hydac_DH_AS)
Type: Active_site

A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown to be structurally related. The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the α-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown to be involved in the removal of the proton. The region around this active site residue is highly conserved and contains an arginine residue which is involved in substrate binding.