SII-SWORD/CoKE huggingface dataset:
Exosome complex component Rrp41 (Rrp41)
Type: Family

The archaeal exosome is a protein complex involved in the degradation and the posttranscriptional tailing of RNA . It degrades single-stranded RNA (ssRNA) in the 3'-5' direction, but also can catalyze the reverse reaction of adding nucleoside diphosphates to the 3'-end of RNA which has been shown to lead to the formation of poly-A-rich tails on RNA .

Rrp41 is a major subunit of the exosome, helping form the catalytic core . Rrp41 is a member of the RNase PH family, named after the bacterial ribonuclease PH, a 3'-5' exoribonuclease. Structurally all members of this family form hexameric rings (trimers of dimers). In archaea, the ring is formed by three Rrp41:Rrp42 dimers. The central chamber within the ring contains three phosphorolytic active sites located in an Rrp41 pocket at the interface between Rrp42 and Rrp41. The ring is capped by three copies of Rrp4 and/or Csl4 which contain putative RNA interaction domains .
Sulphite reductase, dissimilatory-type beta subunit (DsrB)
Type: Family

Dissimilatory sulphite reductase catalyzes the six-electron reduction of sulphite to sulphide, as the terminal reaction in dissimilatory sulphate reduction. It remains unclear however, whether trithionate and thiosulphate serve as intermediate compounds to sulphide, or as end products of sulphite reduction . Sulphite reductase is a multisubunit enzyme composed of dimers of either alpha/beta or alpha/beta/gamma subunits, each containing a siroheme and iron sulphur cluster prosthetic centre . Found in sulphate-reducing bacteria, these genes are commonly located in a unidirectional gene cluster . This entry describes the beta subunit of sulphite reductase.
Histidinol-phosphate phosphatase, putative, inositol monophosphatase (His_9_proposed)
Type: Family

This entry contains proteins that belong to the inositol monophosphatase family. The members of this family consist of no more than one per species and are found only in species in which histidine is synthesized de novo but no histidinol phosphatase can be found in either of the two described families (

,

). In at least one species, the member of this family is found near known histidine biosynthesis genes.
Cyanophycin synthetase (Cya_phycin_syn)
Type: Family

Cyanophycin is an insoluble storage polymer for carbon, nitrogen, and energy, found in most Cyanobacteria. The polymer has a backbone of L-aspartic acid, with most Asp side chain carboxyl groups attached to L-arginine. The polymer is made by this enzyme, cyanophycin synthetase, and degraded by cyanophycinase. Heterologously expressed cyanophycin synthetase in Escherichia coli produces a closely related, water-soluble polymer with some Arg replaced by Lys. It is unclear whether enzymes that produce soluble cyanophycin-like polymers in vivo in non-Cyanobacterial species should be designated as cyanophycin synthetase itself or as a related enzyme. Cyanophycin synthesis is analogous to polyhydroxyalkanoic acid (PHA) biosynthesis, except that PHA polymers lack nitrogen and may be made under nitrogen-limiting conditions .
Peptidase S51, cyanophycinase (Peptidase_S51_cyanophycinase)
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 entry describes both cytosolic and extracellular cyanophycinases. These are serine exopeptidases that hydrolyse alpha-aspartyl bonds and belonging to MEROPS peptidase family S51, clan PC. They are part of a system in many Cyanobacteria and a few other species of generating and later utilizing a storage polymer for nitrogen, carbon, and energy, called cyanophycin. The latter are found in species such as Pseudomonas anguilliseptica that can use external cyanophycin. The polymer has a backbone of L-aspartic acid, with most Asp side chain carboxyl groups attached to L-arginine.
Biosynthetic peptidoglycan transglycosylase (Pep_trsgly)
Type: Family

This family is one of the transglycosylases involved in the late stages of peptidoglycan biosynthesis. Members tend to be small, about 240 amino acids in length, and consist almost entirely of a domain, which describes transglycosylases. Species with this protein will have several other transglycosylases as well. All species with this protein are proteobacteria that produce murein (peptidoglycan).
Penicillin-binding protein 1B (PBP_1b)
Type: Family

Bacterial that synthesize a cell wall of peptidoglycan (murein) generally have several transglycosylases and transpeptidases for the task. This family consists of a particular bifunctional transglycosylase/transpeptidase in Escherichia coli and other Proteobacteria, designated penicillin-binding protein 1B. It's structure has been resolved .
Malonyl-[acyl-carrier protein] O-methyltransferase BioC (BioC)
Type: Family

Malonyl-[acyl-carrier protein] O-methyltransferase BioC is a biotin synthesis protein that converts the free carboxyl group of a malonyl-thioester to its methyl ester by transfer of a methyl group from S-adenosyl-L-methionine (SAM). It allows to synthesize pimeloyl-ACP via by a modified fatty acid synthetic pathway .
Penicillin-binding protein 1C (PBP_1c)
Type: Family

This entry contains penicillin binding proteins includes the member from Escherichia coli designated penicillin-binding protein 1C. Members have both transglycosylase and transpeptidase domains and are involved in forming cross-links in the late stages of peptidoglycan biosynthesis. All members of this entry are presumed to have the same basic function.
Uridylate kinase (Uridylate_kinase)
Type: Family

Uridylate kinases (also known as UMP kinases) are key enzymes in the synthesis of nucleoside triphosphates. They catalyse the reversible transfer of the gamma-phosphoryl group from an ATP donor to UMP, yielding UDP, which is the starting point for the synthesis of all other pyrimidine nucleotides. The eukaryotic enzyme has a dual specificity, phosphorylating both UMP and CMP, while the bacterial enzyme is specific to UMP. The bacterial enzyme shows no sequence similarity to the eukaryotic enzyme or other nucleoside monophosphate kinases, but rather appears to be part of the amino acid kinase family. It is dependent on magnesium for activity and is activated by GTP and repressed by UTP . In many bacterial genomes, the gene tends to be located immediately downstream of elongation factor T and upstream of ribosome recycling factor. A related protein family, believed to be equivalent in function is found in the archaea and in spirochetes.

Structurally, the bacterial and archaeal proteins are homohexamers centred around a hollow nucleus and organised as a trimer of dimers . Each monomer within the protein forms the amino acid kinase fold and can be divided into an N-terminal region which binds UMP and mediates intersubunit interactions within the dimer, and a C-terminal region which binds ATP and contains a mobile loop covering the active site. Inhibition of enzyme activity by UTP appears to be due to competition for the binding site for UMP, not allosteric inhibition as was previously suspected.

This entry represents both the bacterial and archaeal enzymes.
Uridylate kinase, archaeal/spirochete, putative (Uridylate_kinase_arch/spir)
Type: Family

Uridylate kinases (also known as UMP kinases) are key enzymes in the synthesis of nucleoside triphosphates. They catalyse the reversible transfer of the gamma-phosphoryl group from an ATP donor to UMP, yielding UDP, which is the starting point for the synthesis of all other pyrimidine nucleotides. The eukaryotic enzyme has a dual specificity, phosphorylating both UMP and CMP, while the bacterial enzyme is specific to UMP. The bacterial enzyme shows no sequence similarity to the eukaryotic enzyme or other nucleoside monophosphate kinases, but rather appears to be part of the amino acid kinase family. It is dependent on magnesium for activity and is activated by GTP and repressed by UTP . In many bacterial genomes, the gene tends to be located immediately downstream of elongation factor T and upstream of ribosome recycling factor. A related protein family, believed to be equivalent in function is found in the archaea and in spirochetes.

Structurally, the bacterial and archaeal proteins are homohexamers centred around a hollow nucleus and organised as a trimer of dimers . Each monomer within the protein forms the amino acid kinase fold and can be divided into an N-terminal region which binds UMP and mediates intersubunit interactions within the dimer, and a C-terminal region which binds ATP and contains a mobile loop covering the active site. Inhibition of enzyme activity by UTP appears to be due to competition for the binding site for UMP, not allosteric inhibition as was previously suspected.

This entry represents the archaeal and spirochete proteins.
Pyrococcus aspartate kinase subunit, putative (AspKin_pair)
Type: Family

This family consists of proteins restricted to and found as paralogous pairs (typically close together) in species of Pyrococcus, a hyperthermophilic archaeal genus. Members are always found close to other genes of threonine biosynthesis and appear to represent the Pyrococcal form of aspartate kinase. Alignment to aspartokinase III from Escherichia coli shows that 300 N-terminal and 20 C-terminal amino acids are homologous, but the form in Pyrococcus lacks ~100 amino acids in between.
L-threonine dehydratase biosynthetic IlvA (IlvA)
Type: Family

Threonine dehydratase (

) (TDH) catalyzes the dehydratation of threonine into alpha-ketobutarate and ammonia. In Escherichia coli and other microorganisms, two classes of TDH are known to exist. One is involved in the biosynthesis of isoleucine, the other in hydroxamino acid catabolism.

This entry describes a form of TDH that is distinct from the clades described by

and

. The sequences described by this entry have one copy of the threonine dehydratase C-terminal domain (

). They are exclusively found in species containing the rest of the isoleucine biosynthesis pathway and which are generally lacking in members of the other two clades of threonine dehydratases. They include mitochondrial and plastid threonine dehydratases.
O-succinylhomoserine (thiol)-lyase (O_succ_thio_ly)
Type: Family

This family consists of O-succinylhomoserine (thiol)-lyase, one of three different enzymes designated cystathionine gamma-synthase and involved in methionine biosynthesis. In all three cases, sulphur is added by transsulphuration from Cys to yield cystathionine rather than by a sulphhydrylation step that uses H2S directly and bypasses cystathionine.

The CGS enzyme (

) from Escherichia coli is, like other CGS enzymes, a homotetramer composed of two catalytically active dimers . The active site of each dimer is found at the interface between the monomers and involves residues from each monomer. Catalysis occurs by alpha,gamma-elimination/replacement reactions.
Cobalamin-dependent methionine synthase (MetH)
Type: Family

Cobalamin (vitamin B12) dependent methionine synthase

(MetH; 5-methyltetrahydrofolate--homocysteine S-methyltransferase) catalyses the conversion of 5-methyltetrahydrofolate and L-homocysteine to tetrahydrofolate and L-methionine as the final step in
de novo
methionine biosynthesis. The enzyme requires methylcobalamin as a cofactor. In humans, defects in this enzyme are the cause of autosomal recessive inherited methylcobalamin deficiency (CBLG), which causes mental retardation, macrocytic anemia and homocystinuria. Mild deficiencies in activity may result in mild hyperhomocysteinemia, and mutations in the enzyme may be involved in tumorigenesis. Vitamin B12 dependent methionine synthase is found in prokaryotes and eukaryotes, but in prokaryotes the cofactor is cobalamin.

This enzyme is a large protein composed of four structurally and functionally distinct modules: the first two modules bind homocysteine and tetrahydrofolate , the third module binds the B12 cofactor , and the C-terminal module (activation domain) binds S-adenosylmethionine. The activation domain is essential for the reductive activation of the enzyme. During the catalytic cycle, the highly reactive cob(I)alamin intermediate can be oxidised to produce an inactive cob(II)alamin enzyme; the enzyme is then reactivated via reductive methylation by the activation domain . The activation domain adopts an unusual α/β fold.Recent studies suggest that this enzyme exists as an ensemble of conformations with equilibria dependent on the oxidation and methylation state of the cobalamin and on the concentrations of substrates or products .
3-isopropylmalate dehydratase, large subunit, bacteria (IsopropMal_deHydtase_lsu_bac)
Type: Family

3-isopropylmalate dehydratase (or isopropylmalate isomerase;

) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family . Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S] cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively . LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase

, converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis . Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus . It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast .

This entry represents the large subunit of 3-isopropylmalate dehydratase (LeuC) from prokaryotes. Homoaconitase, aconitase and 3-isopropylmalate dehydratase have similar overall structures and domain organisation . All are dehydratases that bind a [4Fe-4S]-cluster.
Hydrolyase LeuD/DmdB, bacterial (LeuD/DmdB_bac)
Type: Family

This entry includes 3-isopropylmalate dehydratase small subunit LeuD from Heliobacterium modesticaldum and 2,3-dimethylmalate dehydratase small subunit DmdB from Eubacterium barkeri . The structure of the Pyrococcus horikoshii small subunit (

) has recently been determined . As expected the structure of this polypeptide is similar to that of aconitase domain 4, though one α helix is replaced by a short loop with relatively high temperature factor values. This loop region is thought to be important for substrate recognition. Unlike other aconitase family proteins, this subunit formed a tetramer through disulphide linkages, though it is not expected to interfere with its interaction with the large subunit. These disulphide linkages would be expected to confer thermostability on the enzyme, reflecting the thermophilic lifestyle of the organism.

Homoaconitase, aconitase, and 3-isopropylmalate dehydratase have similar overall structures. All are dehydratases

and bind a [4Fe-4S]-cluster. 3-isopropylmalate dehydratase is split into large (leuC) and small (leuD) chains in eubacteria. Several pairs of archaeal proteins resemble the leuC and leuD pair in length and sequence but even more closely resemble the respective domains of homoaconitase, and their identity is uncertain.
23S rRNA (uracil(747)-C(5))-methyltransferase RlmC (23SrRNA_MeTrfase_RlmC)
Type: Family

This family consists of RNA methyltransferases designated RlmC or RumB, formerly YbjF. Members act on 23S rRNA U747 in Escherichia coli and the equivalent position in other proteobacterial species .
Homoaconitase/3-isopropylmalate dehydratase, large subunit, prokaryotic (HAcnase/IPMdehydase_lsu_prok)
Type: Family

3-isopropylmalate dehydratase (or isopropylmalate isomerase;

) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family . Aconitases are mostly monomeric proteins which share four domains in common and contain a single, labile [4Fe-4S] cluster. Three structural domains (1, 2 and 3) are tightly packed around the iron-sulphur cluster, while a fourth domain (4) forms a deep active-site cleft. The prokaryotic enzyme is encoded by two adjacent genes, leuC and leuD, corresponding to aconitase domains 1-3 and 4 respectively . LeuC does not bind an iron-sulphur cluster. It is thought that some prokaryotic isopropylamalate dehydrogenases can also function as homoaconitase

, converting cis-homoaconitate to homoisocitric acid in lysine biosynthesis . Homoaconitase has been identified in higher fungi (mitochondria) and several archaea and one thermophilic species of bacteria, Thermus thermophilus . It is also found in the higher plant Arabidopsis thaliana, where it is targeted to the chloroplast .

This entry represents the large subunit of 3-isopropylmalate dehydratase (LeuC), as well as homoaconitase enzymes, from prokaryotes. Homoaconitase, aconitase and 3-isopropylmalate dehydratase have similar overall structures and domain organisation . All are dehydratases that bind a [4Fe-4S]-cluster.
Hydrolyase LeuD/HacB/DmdB (LeuD_type2/HacB/DmdB)
Type: Family

This entry is most closely related to the 3-isopropylmalate dehydratase

. It includes methanogen homoaconitase small subunit HacB from Methanocaldococcus jannaschii , 3-isopropylmalate dehydratase small subunit LeuD from Salmonella typhimurium , 2,3-dimethylmalate dehydratase small subunit DmdB from Eubacterium barkeri and AM-toxin AMT8, an aconitase, from Alternaria alternata .
Isopropylmalate/isohomocitrate dehydrogenase (LEU3_arc)
Type: Family

This entry represents a group of archaeal decarboxylating dehydrogenases which include the leucine biosynthesis enzyme 3-isopropylmalate dehydrogenase (LeuB, LEU3) and the methanogenic cofactor CoB biosynthesis enzyme isohomocitrate dehydrogenase (AksF). Both of these have been characterised in Methanococcus janaschii . Sequences from the non-methanogenic archaea are also represented in this entry, presumably LeuB, although phylogenetic trees cannot establish which gene is which in the methanogens.
Tartrate dehydrogenase (TTC_DH)
Type: Family

Tartrate dehydrogenase catalyzes the oxidation of both meso-and (+)-tartrate as well as a D-malate . These enzymes are closely related to the 3-isopropylmalate and isohomocitrate dehydrogenases found in

and

, respectively.
Isopropylmalate/citramalate/homocitrate synthase (LEU1_arch)
Type: Domain

Methanogenic archaea contain three closely related homologues of the 2-isopropylmalate synthases (LeuA) represented by

. Two of these in Methanococcus janaschii (MJ1392 - CimA ; MJ0503 - AksA ) have been characterised as catalyzing alternative reactions leaving the third (MJ1195) as the presumptive LeuA enzyme. CimA is citramalate (2-methylmalate) synthase, which condenses acetyl-CoA with pyruvate. This enzyme is believed to be involved in the biosynthesis of isoleucine in methanogens and possibly other species lacking threonine dehydratase. AksA is a homocitrate synthase which also produces (homo)2-citrate and (homo)3-citrate in the biosynthesis of Coenzyme B which is restricted solely to methanogenic archaea. Methanogens, then should and apparently do contain all three of these enzymes. Unfortunately, phylogenetic trees do not resolve into three unambiguous clades, making assignment of function to particular genes problematic. Other archaea, which lack a threonine dehydratase (mainly Euryarchaeota), should contain both CimA and LeuA genes. This is true for archaeoglobus fulgidis, but not for the Pyrococci which have none in this clade, but one in

and one in

which may fulfil these roles. Proteins from other species, which have only one hit to this entry and lack threonine dehydratase, are very likely to be LeuA enzymes.
Glucose-1-phosphate adenylyltransferase (ADP-Glc_PPase)
Type: Family

This entry represents the GLGC in plants and bacteria.

Glucose-1-phosphate adenylyltransferase (GLGC) catalyses the first committed and rate-limiting step in starch biosynthesis in plants and glycogen biosynthesis in bacteria. It is the enzymatic site for the regulation of storage polysaccharide accumulation in plants and bacteria. The enzyme is a homotetramer .
Glucose-1-phosphate adenylyltransferase, GlgD subunit (GlgDAde_trans)
Type: Family

This family is GlgD, an apparent regulatory protein that appears in an alpha2/beta2 heterotetramer with GlgC (glucose-1-phosphate adenylyltransferase,

) in a subset of bacteria that use GlgC for glycogen biosynthesis.
Alpha-glucan phosphorylase (Agluc_phsphrylas)
Type: Family

This family consists of known phosphorylases, and homologues believed to share the function of using inorganic phosphate to cleave an alpha 1,4 linkage between the terminal glucose residue and the rest of the polymer (maltodextrin, glycogen, etc.). The name of the glucose storage polymer substrate, and therefore the name of this enzyme, depends on the chain lengths and branching patterns. A number of the members of this family have been shown to operate on small maltodextrins, as may be obtained by utilization of exogenous sources. This family represents a distinct clade from the related families: Glycogen/starch/alpha-glucan phosphorylase and Glycosyl transferase, family 35.
Bacterial/plant glycogen synthase (GS/SS)
Type: Family

This entry represents glycogen (GS) and starch synthases (SS) from bacteria and plants. GS and SS are involved in the elongation of the linear chains of glycogen and starch, respectively, by catalysing the transfer of the glucosyl moiety of the activated glucosyl donor (UDP-glucose or ADP-glucose, depending on the organism in question) to the nonreducing ends of a preexisting alpha(1 to 4) glucan primer .