SII-SWORD/CoKE huggingface dataset:
Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase (Glu/Leu/Phe/Val/Trp_DH)
Type: Family

Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

Glutamate dehydrogenases (

,

, and

) (GluDH) are enzymes that catalyse the NAD-and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate . GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction -this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha-keto acids . In rice, glutamate dehydrogenase 3 is mitochondrial.

Leucine dehydrogenase (

) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues . Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.

Phenylalanine dehydrogenase (

) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate .

Valine dehydrogenase (

) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate .

L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ .
Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase, C-terminal (Glu/Leu/Phe/Val/Trp_DH_C)
Type: Domain

Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

Glutamate dehydrogenases (

,

, and

) (GluDH) are enzymes that catalyse the NAD-and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate . GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction -this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha-keto acids . In rice, glutamate dehydrogenase 3 is mitochondrial.

Leucine dehydrogenase (

) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues . Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.

Phenylalanine dehydrogenase (

) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate .

Valine dehydrogenase (

) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate .

L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ .

This entry represents the C-terminal domain of these proteins.
Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase, dimerisation domain (Glu/Leu/Phe/Val/Trp_DH_dimer)
Type: Domain

Glutamate, leucine, phenylalanine, valine and tryptophan dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

Glutamate dehydrogenases (

,

, and

) (GluDH) are enzymes that catalyse the NAD-and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate . GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction -this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha-keto acids . In rice, glutamate dehydrogenase 3 is mitochondrial.

Leucine dehydrogenase (

) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues . Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.

Phenylalanine dehydrogenase (

) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate .

Valine dehydrogenase (

) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate .

L-tryptophan dehydrogenase catalyses the reversible oxidative deamination of L-tryptophan to indole-3-pyruvate in the presence of NAD+ .

This entry represents the dimerisation region of these enzymes.
Methylmalonyl-CoA mutase, alpha chain, catalytic (MMCoA_mutase_a_cat)
Type: Domain

Methylmalonyl-CoA mutase (

) (MCM) is an adenosylcobalamin (vitamin B12) dependent enzyme that catalyses the isomerization between methylmalonyl-CoA and succinyl-CoA. MCM is involved in various catabolic or biosynthetic pathways; for example in human it is involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle; while in some bacteria it is involved in the synthesis of propionate from tricarboxylic acid-cycle intermediates.

Deficiency of MCM in human causes an often fatal disorder of organic acid metabolism termed methylmalonic acidemia. The sequences of eukaryotic and prokaryotic MCM are rather well conserved. In eukaryotes MCM is located in the mitochondrial matrix and is a homodimer of a polypeptide chain of about 710 amino acids. In bacteria MCM is a dimer of two non-identical, yet structurally related chains.

A small degree of similarity is said to exist between MCM and the large subunit of the adenosylcobalamin-dependent enzyme ethanolamine ammonia-lyase, but this similarity is so weak that these two type of enzymes can not be detected by a single pattern.

This entry describes the N-terminal domain of MCM.
Methylmalonyl-CoA mutase, alpha/beta chain, catalytic (MeMalonylCoA_mutase_a/b_cat)
Type: Domain

Methylmalonyl-CoA mutase (

) (MCM) is an adenosylcobalamin (vitamin B12) dependent enzyme that catalyses the isomerization between methylmalonyl-CoA and succinyl-CoA. MCM is involved in various catabolic or biosynthetic pathways; for example in human it is involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle; while in some bacteria it is involved in the synthesis of propionate from tricarboxylic acid-cycle intermediates.

Deficiency of MCM in human causes an often fatal disorder of organic acid metabolism termed methylmalonic acidemia. The sequences of eukaryotic and prokaryotic MCM are rather well conserved. In eukaryotes, MCM is located in the mitochondrial matrix and is a homodimer of a polypeptide chain of about 710 amino acids. In bacteria MCM is a dimer of two non-identical, yet structurally related chains.

A small degree of similarity is said to exist between MCM and the large subunit of the adenosylcobalamin-dependent enzyme ethanolamine ammonia-lyase, but this similarity is so weak that these two type of enzymes can not be detected by a single pattern.
Glycoside hydrolase, family 2 (Glyco_hydro_2)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase 2

comprises enzymes with several known activities; beta-galactosidase (

); beta-mannosidase (

); beta-glucuronidase (

).

These enzymes contain a conserved glutamic acid residue which has been shown , in Escherichia coli lacZ (

), to be the general acid/base catalyst in the active site of the enzyme.
Glycoside hydrolase family 2, immunoglobulin-like beta-sandwich (Ig-like_GH2)
Type: Domain

This entry describes the immunoglobulin-like β-sandwich domain .

Glycoside hydrolase family 2

comprises enzymes with several known activities: beta-galactosidase (

); beta-mannosidase (

); beta-glucuronidase (

).

These enzymes contain a conserved glutamic acid residue which has been shown , in Escherichia coli lacZ (

), to be the general acid/base catalyst in the active site of the enzyme.

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
Glycoside hydrolase family 2, catalytic domain (Glyco_hydro_2_cat)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 2

comprises enzymes with several known activities; beta-galactosidase (

); beta-mannosidase (

); beta-glucuronidase (

).

These enzymes contain a conserved glutamic acid residue which has been shown , in Escherichia coli lacZ (

), to be the general acid/base catalyst in the active site of the enzyme.

Beta-galactosidase from E. coli has a TIM-barrel-like core surrounded by four other largely beta domains .
Glycosyl hydrolases family 2, sugar binding domain (Glyco_hydro_2_N)
Type: Domain

Proteins containing this domain include beta-galactosidases, beta-mannosidases and beta-glucuronidases. The domain has a jelly-roll fold .
Cereal seed allergen/trypsin and alpha-amylase inhibitor, conserved site (Allergen/tryp_amyl_inhib_CS)
Type: Conserved_site

The seeds of cereals contain numerous serine protease and alpha-amylase inhibitors. These inhibitors can be grouped into families based on structural similarities. This domain identifies sequences belonging to the cereal (monocotyledon) trypsin/alpha-amylase inhibitor family . It includes those annotated solely as seed allergens or alpha-amyalse inhibitors . Many belong to MEROPS inhibitor family I6, clan IJ. Some are known to be inhibit trypsin (an S1 peptidase,

) . For some there is no direct evidence to suggest they any can inhibit trypsin or any other serine peptidase. Studies on the alpha-amylase inhibitor from Secale cereale (Rye) has demonstrated no activity against trypsin, and illustrates the necessity of exercising caution in assigning function based on sequence comparisons .
Cereal seed allergen/grain softness/trypsin and alpha-amylase inhibitor (Allergen/soft/tryp_amyl_inhib)
Type: Family

The seeds of cereals contain numerous serine protease and alpha-amylase inhibitors. These inhibitors can be grouped into families based on structural similarities and many are described as seed allergens. This family of cereal (monocotyledon) allergens, trypsin/alpha-amylase inhibitors belong to MEROPS inhibitor family I6, clan IJ. Some are known to be serine protease inhibitors, active against S1 peptidases (

) . For some there is no direct evidence to suggest they any can inhibit serine peptidases and studies on the alpha-amylase inhibitor from Secale cereale (Rye) demonstrates no activity against trypsin, and illustrates the necessity of exercising caution in assigning function based on sequence comparisons .

They consists of proteins of about 120 amino acids which contain 10 cysteine residues, all of which are involved in disulphide bonds. Some of these inhibitors are specific to trypsin, others to alpha-amylase, and a few are bifunctional. The schematic representation of the structure of these inhibitors is shown below:

+----------------------------+
+----------+| +-+ |
| || | | |
xxCxxxxxxCxxxCxxxxxxCCxxxCxCxxxxxxxxxxxxxCxxxxxxxxCxxxxxxxCxxxx
| | | |
| +---------------------------+ |
+-------------------------------------------------------+

'C': conserved cysteine involved in a disulphide bond.

The 3D structure of the bifunctional alpha-amylase/trypsin inhibitor (RBI) from seeds of Eleusine coracana (Indian finger millet) has been determined in solution using multidimensional 1H and 15N NMR spectroscopy . The inhibitor forms a globular 4-helix motif with a simple 'up-and-down' topology, and includes a short anti-parallel β-sheet .
3-hydroxyacyl-CoA dehydrogenase, C-terminal (3HC_DH_C)
Type: Domain

3-hydroxyacyl-CoA dehydrogenase (

) (HCDH) is an enzyme involved in fatty acid metabolism, it catalyses the reduction of 3-hydroxyacyl-CoA to 3-oxoacyl-CoA. Most eukaryotic cells have 2 fatty-acid beta-oxidation systems, one located in mitochondria and the other in peroxisomes. In peroxisomes 3-hydroxyacyl-CoA dehydrogenase forms, with enoyl-CoA hydratase (ECH) and 3,2-trans-enoyl-CoA isomerase (ECI) a multifunctional enzyme where the N-terminal domain bears the hydratase/isomerase activities and the C-terminal domain the dehydrogenase activity. There are two mitochondrial enzymes: one which is monofunctional and the other which is, like its peroxisomal counterpart, multifunctional.

In Escherichia coli (gene fadB) and Pseudomonas fragi (gene faoA) HCDH is part of a multifunctional enzyme which also contains an ECH/ECI domain as well as a 3-hydroxybutyryl-CoA epimerase domain .

There are two major region of similarities in the sequences of proteins of the HCDH family, the first one located in the N-terminal, corresponds to the NAD-binding site, the second one is located in the centre of the sequence. This represents the C-terminal domain which is also found in lambda crystallin. Some proteins include two copies of this domain.
Glycerol-3-phosphate dehydrogenase, NAD-dependent, C-terminal (G3P_DH_NAD-dep_C)
Type: Domain

NAD-dependent glycerol-3-phosphate dehydrogenase (

) (GPD) catalyzes the reversible reduction of dihydroxyacetone phosphate to glycerol-3-phosphate. It is a cytoplasmic protein, active as a homodimer , each monomer containing an N-terminal NAD binding site . In insects, it acts in conjunction with a mitochondrial alpha-glycerophosphate oxidase in the alpha-glycerophosphate cycle, which is essential for the production of energy used in insect flight .
RNA polymerase, subunit omega/Rpo6/RPB6 (Pol_omega/Rpo6/RPB6)
Type: Family

In eukaryotes, there are three different forms of DNA-dependent RNA polymerases (

) transcribing different sets of genes. Each class of RNA polymerase is an assemblage of ten to twelve different polypeptides. In archaebacteria, there is generally a single form of RNA polymerase which also consists of an oligomeric assemblage of 10 to 13 polypeptides. A component of 14 to 18kDa shared by all three forms of eukaryotic RNA polymerases and which has been sequenced in budding yeast (gene RPB6 or RPO26), in Schizosaccharomyces pombe (Fission yeast) (gene rpb6 or rpo15), in human and in African swine fever virus (ASFV) is evolutionary related to the archaebacterial subunit Rpo6 (also known as subunit K). The archaebacterial protein is colinear with the C-terminal part of the eukaryotic subunit.

The structures of the omega subunit and RBP6, and the structures of the omega/beta' and RPB6/RPB1 interfaces, suggest a molecular mechanism for the function of omega and RPB6 in promoting RNAP assembly and/or stability. The conserved regions of omega and RPB6 form a compact structural domain that interacts simultaneously with conserved regions of the largest RNAP subunit and with the C-terminal tail following a conserved region of the largest RNAP subunit. The second half of the conserved region of omega and RPB6 forms an arc that projects away from the remainder of the structural domain and wraps over and around the C-terminal tail of the largest RNAP subunit, clamping it in a crevice, and threading the C-terminal tail of the largest RNAP subunit through the narrow gap between omega and RPB6 .
Archaeal Rpo6/eukaryotic RPB6 RNA polymerase subunit (Rpo6/Rpb6)
Type: Family

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.

A RNAP component of 14 to 18kDa is shared by all three forms of eukaryotic RNA polymerases and has been sequenced in budding yeast (gene rpb6 or rpo26), in fission yeast (gene rpb6 or rpo15), in human and in African swine fever virus (ASFV) . It is evolutionary related to archaeal Rpo6 subunit (gene rpoK or rpo6). The archaeal protein is colinear with the C-terminal part of the eukaryotic subunit.

This family includes both eukaryotic Rpb6 and archaeal Rpo6 subunit, also known as subunit K, as well as the evolutionary related RPB6 homologue from ASFV .
6-phosphogluconate dehydrogenase, decarboxylating (6PGDH_Gnd/GntZ)
Type: Family

6-Phosphogluconate dehydrogenase (

) (6PGD) is a key enzyme that produces NADPH by converting 6-phospho D-gluconolactone to D-ribulose 5-phosphate in the pentose phosphate pathways (PPP) . NADPH provides the major reducing power required for lipid production and protecting the cell against oxidative stress. 6PGD has been extensively studied with respect to kinetics, regulation, role in pentose-shunt production of NADPH and lipogenesis, and population genetics . 6PGD is associated with several human disorders including cancer and Alzheimer's disease. The structure of budding yeast 6PGD (also known as Gnd1) has been revealed .

Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved . The protein is a homodimer in which the monomers act independently : each contains a large, mainly α-helical domain and a smaller β-α-β domain, containing a mixed parallel and anti-parallel 6-stranded β sheet . NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket .

Bacillus subtilis contains three classes of 6-phosphogluconate dehydrogenases (6PGD), including Gnd (YqjI), GntZ and YqeC (truncated 6PGD). Gnd (YqjI) and GntZ are included in this entry. YgjiI is NADP+ dependent, while GntZ and YqeC are NAD+-dependent .
6-phosphogluconate dehydrogenase, C-terminal (6PGDH_C)
Type: Domain

6-Phosphogluconate dehydrogenase (

) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) . Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved . The protein is a homodimer in which the monomers act independently : each contains a large, mainly α-helical domain and a smaller β-α-β domain, containing a mixed parallel and anti-parallel 6-stranded β sheet . NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket .
6-phosphogluconate dehydrogenase, NADP-binding (6PGDH_NADP-bd)
Type: Domain

6-Phosphogluconate dehydrogenase (

) (6PGD) is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP) . Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequence are highly conserved . The protein is a homodimer in which the monomers act independently : each contains a large, mainly α-helical domain and a smaller β-α-β domain, containing a mixed parallel and anti-parallel six-stranded β-sheet . NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket .