NAD-dependent malic enzyme catalyzes the oxidative decarboxylation of L-malate to pyruvate in the presence of cations and plays important roles in diverse metabolic pathways such as photosynthesis and lipogenesis.
ACT domains are commonly involved in specifically binding an amino acid or other small ligand ...
11-84
2.72e-07
ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme; Members of this CD belong to the superfamily of ACT regulatory domains. Pairs of ACT domains are commonly involved in specifically binding an amino acid or other small ligand leading to regulation of the enzyme. The ACT domain has been detected in a number of diverse proteins; some of these proteins are involved in amino acid and purine biosynthesis, phenylalanine hydroxylation, regulation of bacterial metabolism and transcription, and many remain to be characterized. ACT domain-containing enzymes involved in amino acid and purine synthesis are in many cases allosteric enzymes with complex regulation enforced by the binding of ligands. The ACT domain is commonly involved in the binding of a small regulatory molecule, such as the amino acids L-Ser and L-Phe in the case of D-3-phosphoglycerate dehydrogenase and the bifunctional chorismate mutase-prephenate dehydratase enzyme (P-protein), respectively. Aspartokinases typically consist of two C-terminal ACT domains in a tandem repeat, but the second ACT domain is inserted within the first, resulting in, what is normally the terminal beta strand of ACT2, formed from a region N-terminal of ACT1. ACT domain repeats have been shown to have nonequivalent ligand-binding sites with complex regulatory patterns such as those seen in the bifunctional enzyme, aspartokinase-homoserine dehydrogenase (ThrA). In other enzymes, such as phenylalanine hydroxylases, the ACT domain appears to function as a flexible small module providing allosteric regulation via transmission of conformational changes, these conformational changes are not necessarily initiated by regulatory ligand binding at the ACT domain itself. ACT domains are present either singularly, N- or C-terminal, or in pairs present C-terminal or between two catalytic domains. Unique to cyanobacteria are four ACT domains C-terminal to an aspartokinase domain. A few proteins are composed almost entirely of ACT domain repeats as seen in the four ACT domain protein, the ACR protein, found in higher plants; and the two ACT domain protein, the glycine cleavage system transcriptional repressor (GcvR) protein, found in some bacteria. Also seen are single ACT domain proteins similar to the Streptococcus pneumoniae ACT domain protein (uncharacterized pdb structure 1ZPV) found in both bacteria and archaea. Purportedly, the ACT domain is an evolutionarily mobile ligand binding regulatory module that has been fused to different enzymes at various times.
The actual alignment was detected with superfamily member cd04887:
Pssm-ID: 471857 Cd Length: 74 Bit Score: 47.67 E-value: 2.72e-07
NAD(P) binding domain of malic enzyme (ME), subgroup 2; Malic enzyme (ME), a member of the ...
237-456
2.13e-83
NAD(P) binding domain of malic enzyme (ME), subgroup 2; Malic enzyme (ME), a member of the amino acid dehydrogenase (DH)-like domain family, catalyzes the oxidative decarboxylation of L-malate to pyruvate in the presence of cations (typically Mg++ or Mn++) with the concomitant reduction of cofactor NAD+ or NADP+. ME has been found in all organisms, and plays important roles in diverse metabolic pathways such as photosynthesis and lipogenesis. This enzyme generally forms homotetramers. The conversion of malate to pyruvate by ME typically involves oxidation of malate to produce oxaloacetate, followed by decarboxylation of oxaloacetate to produce pyruvate and CO2. This subfamily consists primarily of archaeal and bacterial ME. Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.
Pssm-ID: 133453 [Multi-domain] Cd Length: 226 Bit Score: 256.04 E-value: 2.13e-83
ACT_MalLac-Enz CD includes the N-terminal ACT domain of putative NAD-dependent malic enzyme 1, ...
11-84
2.72e-07
ACT_MalLac-Enz CD includes the N-terminal ACT domain of putative NAD-dependent malic enzyme 1, Bacillus subtilis YqkI and related domains; The ACT_MalLac-Enz CD includes the N-terminal ACT domain of putative NAD-dependent malic enzyme 1, Bacillus subtilis YqkI, a malolactic enzyme (MalLac-Enz) which converts malate to lactate, and other related ACT domains. The yqkJ product is predicted to convert malate directly to lactate, as opposed to related malic enzymes that convert malate to pyruvate. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153159 Cd Length: 74 Bit Score: 47.67 E-value: 2.72e-07
NAD(P) binding domain of malic enzyme (ME), subgroup 2; Malic enzyme (ME), a member of the ...
237-456
2.13e-83
NAD(P) binding domain of malic enzyme (ME), subgroup 2; Malic enzyme (ME), a member of the amino acid dehydrogenase (DH)-like domain family, catalyzes the oxidative decarboxylation of L-malate to pyruvate in the presence of cations (typically Mg++ or Mn++) with the concomitant reduction of cofactor NAD+ or NADP+. ME has been found in all organisms, and plays important roles in diverse metabolic pathways such as photosynthesis and lipogenesis. This enzyme generally forms homotetramers. The conversion of malate to pyruvate by ME typically involves oxidation of malate to produce oxaloacetate, followed by decarboxylation of oxaloacetate to produce pyruvate and CO2. This subfamily consists primarily of archaeal and bacterial ME. Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.
Pssm-ID: 133453 [Multi-domain] Cd Length: 226 Bit Score: 256.04 E-value: 2.13e-83
NAD(P) binding domain of malic enzyme; Malic enzyme (ME), a member of the amino acid ...
237-456
2.76e-34
NAD(P) binding domain of malic enzyme; Malic enzyme (ME), a member of the amino acid dehydrogenase (DH)-like domain family, catalyzes the oxidative decarboxylation of L-malate to pyruvate in the presence of cations (typically Mg++ or Mn++) with the concomitant reduction of cofactor NAD+ or NADP+. ME has been found in all organisms and plays important roles in diverse metabolic pathways such as photosynthesis and lipogenesis. This enzyme generally forms homotetramers. The conversion of malate to pyruvate by ME typically involves oxidation of malate to produce oxaloacetate, followed by decarboxylation of oxaloacetate to produce pyruvate and CO2. Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.
Pssm-ID: 133442 Cd Length: 254 Bit Score: 128.87 E-value: 2.76e-34
NAD(P) binding domain of malic enzyme (ME), subgroup 1; Malic enzyme (ME), a member of the ...
239-456
6.00e-24
NAD(P) binding domain of malic enzyme (ME), subgroup 1; Malic enzyme (ME), a member of the amino acid dehydrogenase (DH)-like domain family, catalyzes the oxidative decarboxylation of L-malate to pyruvate in the presence of cations (typically Mg++ or Mn++) with the concomitant reduction of cofactor NAD+ or NADP+. ME has been found in all organisms, and plays important roles in diverse metabolic pathways such as photosynthesis and lipogenesis. This enzyme generally forms homotetramers. The conversion of malate to pyruvate by ME typically involves oxidation of malate to produce oxaloacetate, followed by decarboxylation of oxaloacetate to produce pyruvate and CO2. This subfamily consists of eukaryotic and bacterial ME. Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.
Pssm-ID: 133454 Cd Length: 279 Bit Score: 101.09 E-value: 6.00e-24
ACT_MalLac-Enz CD includes the N-terminal ACT domain of putative NAD-dependent malic enzyme 1, ...
11-84
2.72e-07
ACT_MalLac-Enz CD includes the N-terminal ACT domain of putative NAD-dependent malic enzyme 1, Bacillus subtilis YqkI and related domains; The ACT_MalLac-Enz CD includes the N-terminal ACT domain of putative NAD-dependent malic enzyme 1, Bacillus subtilis YqkI, a malolactic enzyme (MalLac-Enz) which converts malate to lactate, and other related ACT domains. The yqkJ product is predicted to convert malate directly to lactate, as opposed to related malic enzymes that convert malate to pyruvate. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153159 Cd Length: 74 Bit Score: 47.67 E-value: 2.72e-07
C-terminal ACT domain of biodegradative (catabolic) threonine dehydratase II (ThrD-II) and ...
24-81
2.90e-03
C-terminal ACT domain of biodegradative (catabolic) threonine dehydratase II (ThrD-II) and other related ACT domains; This CD includes the C-terminal ACT domain of biodegradative (catabolic) threonine dehydratase II (ThrD-II) and other related ACT domains. The Escherichia coli tdcB gene product, ThrD-II, anaerobically catalyzes the pyridoxal phosphate-dependent dehydration of L-threonine and L-serine to ammonia and to alpha-ketobutyrate and pyruvate, respectively. Tetrameric ThrD-II is subject to allosteric activation by AMP, inhibition by alpha-keto acids, and catabolite inactivation by several metabolites of glycolysis and the citric acid cycle. Also included in this CD are N-terminal ACT domains present in smaller (~170 a.a.) archaeal proteins of unknown function. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153158 [Multi-domain] Cd Length: 73 Bit Score: 36.37 E-value: 2.90e-03
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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