SII-SWORD/CoKE huggingface dataset:
Nitrogen regulatory protein PII/ATP phosphoribosyltransferase, C-terminal (N-reg_PII/ATP_PRibTrfase_C)
Type: Homologous_superfamily

This entry represents a structural domain found in the nitrogen regulatory protein PII, in ATP phosphribosyltransferases (C-terminal domain), and in some bacterial hypothetical proteins. This domain consists of a ferredoxin-like α/β sandwich, which forms trimeric structures with orthogonally packed β-sheets around a three-fold axis.

PII is a tetrameric protein encoded by glnB that functions as a component of the adenylation cascade involved in the regulation of glutamine synthetase activity . PII helps regulate the level of glutamine synthetase in response to nitrogen source availability. In nitrogen-limiting conditions, PII is uridylylated to form PII-UMP, which allows the deadenylation of glutamine synthetase, thus activating the enzyme. Conversely, in nitrogen excess, PI-UMP is deuridylated to PII, promoting the adenylation and deactivation of glutamine synthetase .

ATP phosphoribosyltransferase is the first enzyme of the histidine pathway. It is allosterically regulated, controlling the flow of intermediates through the pathway. The C-terminal domain is the regulatory region of the protein, which binds the allosteric inhibitor histidine .
Glutaminase (Glutaminase)
Type: Family

Glutaminases (

) deaminate glutamine to glutamate. In Bacillus subtilis, glutaminase is encoded by glnA, which is part of an operon, glnA-glnT (formerly ybgJ-ybgH), where glnT encodes a glutamine transporter. The glnA-glnT operon is regulated by the 2-component system GlnK-GlnL in response to glutamine . This entry represents the core structural motif of a family of glutaminases that include GlnA, which are characterised by their beta-lactamase-like topology, containing a cluster of α-helices and an α/β sandwich.

This family describes the enzyme glutaminase, from a larger family that includes serine-dependent beta-lactamases and penicillin-binding proteins. Many bacteria have two isozymes. This model is based on selected known glutaminases and their homologues within prokaryotes, with the exclusion of highly-derived (long branch) and architecturally varied homologues, so as to achieve conservative assignments. A sharp drop in scores occurs below 250, and cutoffs are set accordingly. The enzyme converts glutamine to glutamate, with the release of ammonia. Members tend to be described as glutaminase A (glsA), where B (glsB) is unknown and may not be homologous (as in Rhizobium etli. Some species have two isozymes that may both be designated A (GlsA1 and GlsA2).
Transcription antitermination protein, NusG, bacteria, conserved site (Transcrpt_antiterm_NusG_bac_CS)
Type: Conserved_site

Bacterial transcription antitermination protein, NusG, is a component of the transcription complex and interacts with the termination factor Rho and RNA polymerase . NusG is a bacterial transcriptional elongation factor involved in transcription termination and anti-termination .
UDP-3-O-acyl N-acetylglucosamine deacetylase, N-terminal (UDP-acyl_N-AcGlcN_deAcase_N)
Type: Homologous_superfamily

This entry represents the N-terminal domain which is required for deacetylase activity.

UDP-3-O-N-acetylglucosamine deacetylases are zinc-dependent metalloamidases that catalyse the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram-negative bacteria. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds . The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer α/β structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid . This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents .
Transcription initiation factor IIA, gamma subunit, C-terminal (TFIIA_gsu_C)
Type: Domain

Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP , and can dissociate HMGB1 already bound to TBP/TATA-box.

Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 .

This entry represents the β-barrel domain found at the C-terminal of the gamma subunit of transcription factor TFIIA.
Transcription initiation factor IIA, gamma subunit, N-terminal (TFIIA_gsu_N)
Type: Domain

Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP , and can dissociate HMGB1 already bound to TBP/TATA-box.

Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 .

This entry represents the α-helical domain found at the N-terminal of the gamma subunit of transcription factor TFIIA.
Acyl-CoA desaturase (Acyl-CoA_DS)
Type: Family

Fatty acid desaturases are enzymes that catalyse the insertion of a double bond at the delta position of fatty acids. There seems to be two distinct families of fatty acid desaturases which do not seem to be evolutionary related: the first contains stearoyl-CoA desaturase (SCD), also known as Acyl-CoA desaturase or delta-9 desaturase (

); the second includes plant stearoyl-acyl-carrier protein and cyanobacteria desA protein .

SCD is a key regulatory enzyme of unsaturated fatty acid biosynthesis. In association with cytochrome b5 and NADP-dependent cytochrome b5 reductase, it constitutes part of a microsomal membrane-bound 3-component system in animals and fungi . SCD contains 4 putative transmembrane (TM) regions that anchor it in the microsomal membrane . SCD uses oxygen and electrons from reduced cytochrome b5 to catalyse the insertion of a cis double bond between carbons 9 and 10 of a spectrum of fatty acids . The preferred substrates of SCD are palmitoyl-CoA and stearoyl-CoA, which are converted to palmitoleic (16:1) and oleic (18:1) acids respectively . These unsaturated molecules are the major storage form of fatty acids (as triacylglycerols) in adipocytes .
MAT1, centre (MAT1_centre)
Type: Domain

This entry represents the central region of MAT1.

MAT1 (menage a trois 1) is a RING finger protein with a characteristic C3HC4 motif in its N-terminal domain that plays a crucial role in stabilizing the cyclin H-CDK7 complex, forming the functional CDK-activating kinase (CAK) enzymatic complex responsible for activating many CDK enzymes involved in cell cycle regulation . In vivo, CDK7 forms a stable complex with cyclin H and MAT1 only when phosphorylated at either Ser164 or Thr170 in its T-loop; this phosphorylation can bypass the requirement for MAT1 in CAK activation. While MAT1 addition and T-loop phosphorylation can independently stabilize and activate the CDK7 complex in vitro, under physiological conditions these mechanisms cooperate to maintain complex integrity. Notably, if CDK7 becomes dephosphorylated, even the presence of MAT1 cannot prevent dissociation of the complex into monomeric subunits, especially under prolonged elevated temperatures .
S-adenosyl-L-homocysteine hydrolase, NAD binding domain (Ado_hCys_hydrolase_NAD-bd)
Type: Domain

S-adenosyl-L-homocysteine hydrolase (

) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. AdoHcyase is an ubiquitous enzyme which binds and requires NAD
+
as a cofactor.
AdoHcyase is a highly conserved protein of about 430 to 470 amino acids.
Aromatic-ring-hydroxylating dioxygenase, alpha subunit, C-terminal domain (Ring_hydroxy_dOase_asu_C_dom)
Type: Domain

This entry represents the conserved C-terminal domain found in the alpha subunit of aromatic-ring-hydroxylating dioxygenases. It is the catalytic domain of aromatic-ring- hydroxylating dioxygenase systems. The active site contains a non-heme ferrous ion coordinated by three ligands.

Aromatic ring hydroxylating dioxygenases are multicomponent 1,2-dioxygenase complexes that convert closed-ring structures to non-aromatic cis-diols . The complex has both hydroxylase and electron transfer components. The hydroxylase component is itself composed of two subunits: an alpha-subunit of about 50kDa, and a beta-subunit of about 20kDa. The electron transfer component is either composed of two subunits: a ferredoxin and a ferredoxin reductase or by a single bifunctional ferredoxin/reductase subunit. Sequence analysis of hydroxylase subunits of ring hydroxylating systems (including toluene, benzene and napthalene 1,2-dioxygenases) suggests they are derived from a common ancestor . The alpha-subunit binds both a Rieske-like 2Fe-2S cluster and an iron atom: conserved Cys and His residues in the N-terminal region may provide 2Fe-2S ligands, while conserved His and Tyr residues may coordinate the iron. The beta subunit may be responsible for the substrate specificity of the dioxygenase system .
Aromatic-ring-hydroxylating dioxygenase ARHD, Rieske 2Fe-2S-binding site (ARHD_Rieske_2Fe_2S)
Type: Binding_site

This entry represents the Rieske type 2Fe-2S binding site found at the N-terminal in the alpha-subunit of ARHD proteins and related non-heme iron oxygenases. The Rieske-type [2Fe-2S] cluster is coordinated to its protein by two cysteine residues and two histidine residues .

Aromatic-ring-hydroxylating dioxygenases (ARHD) are multicomponent 1,2-dioxygenase complexes that convert closed-ring structures to non-aromatic cis-diols . The complex has both hydroxylase and electron transfer components. The hydroxylase component is composed of two subunits: an alpha-subunit of about 50 kDa and a beta-subunit of about 20 kDa. The electron transfer component is either composed of two subunits: a ferredoxin and a ferredoxin reductase or by a single bifunctional ferredoxin/reductase subunit. Sequence analysis of hydroxylase subunits of ring hydroxylating systems (including toluene, benzene, and napthalene 1,2-dioxygenases) suggests they are derived from a common ancestor . The alpha-subunit binds both a Rieske-like 2Fe-2S cluster and an iron atom: conserved Cys and His residues in the N-terminal region may provide 2Fe-2S ligands, while conserved His and Tyr residues may coordinate the iron. The beta subunit may be responsible for the substrate specificity of the dioxygenase system .
Beta-hexosaminidase, bacterial type, N-terminal (HEX_bac_N)
Type: Domain

This entry represents the N-terminal domain of the beta-hexosaminidases mostly from bacteria, some yeasts and invertebrates. This domain has a zincin-like fold and can be found in chitobiases, hyaluronoglucosaminidases, N,N'-diacetylchitobiases and O-GlcNAcase NagJ. They belong to either the glycosyl hydrolase 84 or the glycosyl hydrolase 20 families.
Glycoside hydrolase family 20, catalytic domain (Glyco_hydro_20_cat)
Type: Domain

Glycoside hydrolase family 20 (

) comprises enzymes with several known activities; beta-hexosaminidase (

); lacto-N-biosidase (

); beta-1,6-N-acetylglucosaminidase); and beta-6-SO3-N-acetylglucosaminidase. Carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base in this family of enzymes .

This entry represents the glycoside hydrolase family 20 catalytic domain. This domain has a TIM barrel fold.
Malic enzyme, conserved site (Malic_enzyme_CS)
Type: Conserved_site

Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate, a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis . There are 3 forms of the enzyme : an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form . Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase ; and the hypothetical Saccharomyces cerevisiae protein YKL029c.

Studies on the duck liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity . The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate-or divalent metal ion-binding in the active site . Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme , although it is absent in the sequences from some species.

There are three well conserved regions in the enzyme sequences. Two of them seem to be involved in the binding NAD or NADP. This entry represents the conserved region, located in the central part of the enzymes, its function is not yet known.
Formamidopyrimidine-DNA glycosylase, H2TH DNA-binding (H2TH_FPG)
Type: Domain

This entry represents a helix-2-turn-helix DNA-binding domain found in DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents.

Formamidopyrimidine-DNA glycosylases (Fpg, MutM) are trifunctional DNA base excision repair enzymes that remove a wide range of oxidation-damaged bases (N-glycosylase activity;

) and cleave both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity;

). Fpg has a preference for oxidised purines, excising oxidised purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). Its AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge . The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidised base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes . Fpg binds one ion of zinc at the C-terminal, which contains four conserved and essential cysteines .

Endonuclease VIII (Nei) has the same enzyme activities as Fpg (

,

), but with a preference for oxidised pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine . These proteins contain three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger . The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. Residues that contact DNA are located in the catalytic domain and in a β-hairpin loop formed by the zinc finger .
L-fucose isomerase, C-terminal (Fuc_isomerase_C)
Type: Domain

L-fucose isomerase (

) converts the aldose L-fucose into the corresponding ketose L-fuculose during the first step in fucose metabolism using Mn2+ as a cofactor. The enzyme is a hexamer, forming the largest structurally known ketol isomerase, and has no sequence or structural similarity with other ketol isomerases. The structure was determined by X-ray crystallography at 2.5 A resolution .
Intradiol ring-cleavage dioxygenase, core (Intradiol_dOase_core)
Type: Homologous_superfamily

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes (

) use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) . These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues.

Enzymes that belong to the intradiol family include catechol 1,2-dioxygenase (1,2-CTD) (

); protocatechuate 3,4-dioxygenase (3,4-PCD) (

); and chlorocatechol 1,2-dioxygenase (

) .
Chorismate-utilising enzyme, C-terminal (Chorismate_C)
Type: Domain

This entry represents the catalytic regions of the chorismate binding enzymes anthranilate synthase, isochorismate synthase, aminodeoxychorismate synthase and para-aminobenzoate synthase . Anthranilate synthase catalyses the reaction:
chorismate + l-glutamine = anthranilate + pyruvate + l-glutamate.
The enzyme is a tetramer comprising 2 I and 2 II components: this entry is restricted to component I that catalyses the formation of anthranilate using ammonia rather than glutamine, while component II provides glutamine amidotransferase activity.
Carbonic anhydrase, prokaryotic-like, conserved site (Carbonic_anhydrase_CS)
Type: Conserved_site

Carbonic anhydrases (

) (CA) are zinc metalloenzymes which catalyze the reversible hydration of carbon dioxide.
In Escherichia coli, CA (gene cynT) is involved in recycling carbon dioxide formed in the bicarbonate-dependent decomposition of cyanate by cyanase (gene cynS). By this action, it prevents the depletion of cellular bicarbonate . In photosynthetic bacteria and plant chloroplast, CA is essential to inorganic carbon fixation .
Prokaryotic and plant chloroplast CA are structurally and evolutionary related and form a family distinct from the one which groups the many different forms of eukaryotic CA's (see

).
Hypothetical proteins yadF from Escherichia coli and HI1301 from Haemophilus influenzae also belong to this family.
Guanylate-binding protein, N-terminal (Guanylate-bd_N)
Type: Domain

Guanylate-binding protein is a GTPase that is induced by interferon (IFN)-gamma. GTPases induced by IFN-gamma are key to the protective immunity against microbial and viral pathogens. These GTPases are classified into three groups: the small 47-kd GTPases, the Mx proteins, and the large 65- to 67-kd GTPases. Guanylate-binding proteins (GBP) fall into the last class. In humans, there are seven GBPs (hGBP1-7) . Structurally, hGBP1 consists of two domains: a compact globular N-terminal domain harbouring the GTPase function, and an α-helical finger-like C-terminal domain (

). Human GBP1 is secreted from cells without the need of a leader peptide, and has been shown to exhibit antiviral activity against Vesicular stomatitis virus and Encephalomyocarditis virus, as well as being able to regulate the inhibition of proliferation and invasion of endothelial cells in response to IFN-gamma .
Glutamyl-tRNA reductase, N-terminal (4pyrrol_synth_GluRdtase_N)
Type: Domain

This entry represents the N-terminal domain of glutamyl-tRNA reductase (

), which reduces glutamyl-tRNA to glutamate-1-semialdehyde during the first stage of tetrapyrrole biosynthesis by the C5 pathway . The enzyme requires NADPH as a cofactor. This N-terminal domain is the catalytic domain .
Tetrapyrrole biosynthesis, glutamyl-tRNA reductase, dimerisation domain (4pyrrol_synth_GluRdtase_dimer)
Type: Domain

Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway . The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin .

The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase (

), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase (

) to charge a tRNA with glutamate, glutamyl-tRNA reductase (

) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase (

) to catalyse a transamination reaction to produce ALA.

The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase,

) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase,

) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase (

) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.

Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase (

). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase (

) .

This entry represents the helical dimerisation domain of glutamyl-tRNA reductase (

) . This enzyme reduces glutamyl-tRNA to glutamate-1-semialdehyde during the first stage of tetrapyrrole biosynthesis by the C5 pathway . The enzyme requires NADPH as a cofactor.
CHK kinase-like (CHK_kinase-like)
Type: Domain

Zinc finger C4 and HLH domain containing kinases domain subfamily of choline kinases.
UDP-galactopyranose mutase, C-terminal (UDP-GalPyranose_mutase_C)
Type: Domain

UDP-galactopyranose mutase (

) is involved in the conversion of UDP-GALP into UDP-GALF through a 2-keto intermediate, and contains FAD as a cofactor. The gene is known as glf, ceoA, and rfbD. It is known experimentally in Escherichia coli, Mycobacterium tuberculosis, and Klebsiella pneumoniae.