2-isopropylmalate synthase, bacterial type; This is the first enzyme of leucine biosynthesis. ...
4-501
0e+00
2-isopropylmalate synthase, bacterial type; This is the first enzyme of leucine biosynthesis. A larger family of homologous proteins includes homocitrate synthase, distinct lineages of 2-isopropylmalate synthase, several distinct, uncharacterized, orthologous sets in the Archaea, and other related enzymes. This model describes a family of 2-isopropylmalate synthases found primarily in Bacteria. The homologous families in the Archaea may represent isozymes and/or related enzymes. [Amino acid biosynthesis, Pyruvate family]
Pssm-ID: 130046 [Multi-domain] Cd Length: 494 Bit Score: 674.55 E-value: 0e+00
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
3-472
0e+00
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis
Pssm-ID: 439889 [Multi-domain] Cd Length: 452 Bit Score: 614.48 E-value: 0e+00
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ...
7-276
1.53e-174
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163678 Cd Length: 268 Bit Score: 491.96 E-value: 1.53e-174
LeuA allosteric (dimerisation) domain; This is the C-terminal regulatory (R) domain of ...
371-489
2.47e-38
LeuA allosteric (dimerisation) domain; This is the C-terminal regulatory (R) domain of alpha-isopropylmalate synthase, which catalyses the first committed step in the leucine biosynthetic pathway. This domain, is an internally duplicated structure with a novel fold. It comprises two similar units that are arranged such that the two -helices pack together in the centre, crossing at an angle of 34 degrees, sandwiched between the two three-stranded, antiparallel beta-sheets. The overall domain is thus constructed as a beta-alpha-beta three-layer sandwich.
Pssm-ID: 214910 [Multi-domain] Cd Length: 131 Bit Score: 136.46 E-value: 2.47e-38
2-isopropylmalate synthase, bacterial type; This is the first enzyme of leucine biosynthesis. ...
4-501
0e+00
2-isopropylmalate synthase, bacterial type; This is the first enzyme of leucine biosynthesis. A larger family of homologous proteins includes homocitrate synthase, distinct lineages of 2-isopropylmalate synthase, several distinct, uncharacterized, orthologous sets in the Archaea, and other related enzymes. This model describes a family of 2-isopropylmalate synthases found primarily in Bacteria. The homologous families in the Archaea may represent isozymes and/or related enzymes. [Amino acid biosynthesis, Pyruvate family]
Pssm-ID: 130046 [Multi-domain] Cd Length: 494 Bit Score: 674.55 E-value: 0e+00
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; ...
3-472
0e+00
Isopropylmalate/homocitrate/citramalate synthases [Amino acid transport and metabolism]; Isopropylmalate/homocitrate/citramalate synthases is part of the Pathway/BioSystem: Isoleucine, leucine, valine biosynthesis
Pssm-ID: 439889 [Multi-domain] Cd Length: 452 Bit Score: 614.48 E-value: 0e+00
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate ...
7-276
1.53e-174
2-isopropylmalate synthase (IPMS), N-terminal catalytic TIM barrel domain; 2-isopropylmalate synthase (IPMS) catalyzes an aldol-type condensation of acetyl-CoA and 2-oxoisovalerate yielding 2-isopropylmalate and CoA, the first committed step in leucine biosynthesis. This family includes the Arabidopsis thaliana IPMS1 and IPMS2 proteins, the Glycine max GmN56 protein, and the Brassica insularis BatIMS protein. This family also includes a group of archeal IPMS-like proteins represented by the Methanocaldococcus jannaschii AksA protein. AksA catalyzes the condensation of alpha-ketoglutarate and acetyl-CoA to form trans-homoaconitate, one of 13 steps in the conversion of alpha-ketoglutarate and acetylCoA to alpha-ketosuberate, a precursor to coenzyme B and biotin. AksA also catalyzes the condensation of alpha-ketoadipate or alpha-ketopimelate with acetylCoA to form, respectively, the (R)-homocitrate homologs (R)-2-hydroxy-1,2,5-pentanetricarboxylic acid and (R)-2-hydroxy-1,2,6- hexanetricarboxylic acid. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163678 Cd Length: 268 Bit Score: 491.96 E-value: 1.53e-174
isopropylmalate/citramalate/homocitrate synthases; Methanogenic archaea contain three closely ...
7-381
7.40e-130
isopropylmalate/citramalate/homocitrate synthases; Methanogenic archaea contain three closely related homologs of the 2-isopropylmalate synthases (LeuA) represented by TIGR00973. Two of these in Methanococcus janaschii (MJ1392 - CimA; MJ0503 - AksA) have been characterized 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 aparrently 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 a CimA and a LeuA gene. This is true of, for example, archaeoglobus fulgidis, but not for the Pyrococci which have none in this clade, but one in TIGR00973 and one in TIGRT00977 which may fulfill these roles. Other species which have only one hit to this model and lack threonine dehydratase are very likely LeuA enzymes.
Pssm-ID: 273964 [Multi-domain] Cd Length: 363 Bit Score: 382.22 E-value: 7.40e-130
homocitrate synthase NifV; This family consists of the NifV clade of homocitrate synthases, ...
4-381
3.27e-94
homocitrate synthase NifV; This family consists of the NifV clade of homocitrate synthases, most of which are found in operons for nitrogen fixation. Members are closely homologous to enzymes that include 2-isopropylmalate synthase, (R)-citramalate synthase, and homocitrate synthases associated with other processes. The homocitrate made by this enzyme becomes a part of the iron-molybdenum cofactor of nitrogenase. [Biosynthesis of cofactors, prosthetic groups, and carriers, Other, Central intermediary metabolism, Nitrogen fixation]
Pssm-ID: 274248 [Multi-domain] Cd Length: 365 Bit Score: 290.72 E-value: 3.27e-94
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes ...
8-276
6.83e-91
DRE-TIM metallolyase superfamily; The DRE-TIM metallolyase superfamily includes 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163674 [Multi-domain] Cd Length: 265 Bit Score: 278.57 E-value: 6.83e-91
Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) ...
7-277
4.45e-73
Streptomyces rubellomurinus FrbC and related proteins, catalytic TIM barrel domain; FrbC (NifV) of Streptomyces rubellomurinus catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate and CoA, a reaction similar to one catalyzed by homocitrate synthase. The gene encoding FrbC is one of several genes required for the biosynthesis of FR900098, a potent antimalarial antibiotic. This protein is also required for assembly of the nitrogenase MoFe complex but its exact role is unknown. This family also includes the NifV proteins of Heliobacterium chlorum and Gluconacetobacter diazotrophicus, which appear to be orthologous to FrbC. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163677 [Multi-domain] Cd Length: 259 Bit Score: 232.40 E-value: 4.45e-73
citramalate synthase; This model includes GSU1798 and is now known to represent citramalate ...
4-489
2.31e-51
citramalate synthase; This model includes GSU1798 and is now known to represent citramalate synthase. Members are related to 2-isopropylmalate synthases and homocitrate synthases but phylogenetically distinct. The role is isoleucine biosynthesis, the first dedicated step. [Unknown function, General]
Pssm-ID: 130050 [Multi-domain] Cd Length: 526 Bit Score: 183.18 E-value: 2.31e-51
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic ...
9-289
7.19e-45
Leptospira interrogans citramalate synthase (CMS) and related proteins, N-terminal catalytic TIM barrel domain; Citramalate synthase (CMS) catalyzes the conversion of pyruvate and acetyl-CoA to (R)-citramalate in the first dedicated step of the citramalate pathway. Citramalate is only found in Leptospira interrogans and a few other microorganisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163683 [Multi-domain] Cd Length: 280 Bit Score: 159.08 E-value: 7.19e-45
Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel ...
7-242
4.06e-42
Desulfobacterium autotrophicum LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; Desulfobacterium autotrophicum LeuA3 is sequence-similar to alpha-isopropylmalate synthase (LeuA) but its exact function is unknown. Members of this family have an N-terminal TIM barrel domain that belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163679 Cd Length: 273 Bit Score: 151.45 E-value: 4.06e-42
LeuA allosteric (dimerisation) domain; This is the C-terminal regulatory (R) domain of ...
371-489
2.47e-38
LeuA allosteric (dimerisation) domain; This is the C-terminal regulatory (R) domain of alpha-isopropylmalate synthase, which catalyses the first committed step in the leucine biosynthetic pathway. This domain, is an internally duplicated structure with a novel fold. It comprises two similar units that are arranged such that the two -helices pack together in the centre, crossing at an angle of 34 degrees, sandwiched between the two three-stranded, antiparallel beta-sheets. The overall domain is thus constructed as a beta-alpha-beta three-layer sandwich.
Pssm-ID: 214910 [Multi-domain] Cd Length: 131 Bit Score: 136.46 E-value: 2.47e-38
Mycobacterium tuberculosis LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; ...
10-263
7.99e-36
Mycobacterium tuberculosis LeuA3 and related proteins, N-terminal catalytic TIM barrel domain; Alpha-isopropylmalate synthase (LeuA), a key enzyme in leucine biosynthesis, catalyzes the first committed step in the pathway, converting acetyl-CoA and alpha-ketoisovalerate to alpha-isopropyl malate and CoA. Although the reaction catalyzed by LeuA is similar to that of the Arabidopsis thaliana IPMS1 protein, the two fall into phylogenetically distinct families within the same superfamily. LeuA has and N-terminal TIM barrel catalytic domain, a helical linker domain, and a C-terminal regulatory domain. LeuA forms a homodimer in which the linker domain of one monomer sits over the catalytic domain of the other, inserting residues into the active site that may be important for catalysis. Homologs of LeuA are found in bacteria as well as fungi. This family includes alpha-isopropylmalate synthases I (LEU4) and II (LEU9) from Saccharomyces cerevisiae. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163680 Cd Length: 284 Bit Score: 134.62 E-value: 7.99e-36
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel ...
7-246
6.75e-35
Saccharomyces cerevisiae homocitrate synthase and related proteins, catalytic TIM barrel domain; Homocitrate synthase (HCS) catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica LYS1 protein as well as the Saccharomyces cerevisiae LYS20 and LYS21 proteins. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163685 Cd Length: 262 Bit Score: 131.69 E-value: 6.75e-35
LeuA allosteric (dimerization) domain; This is the C-terminal regulatory (R) domain of ...
393-489
2.01e-30
LeuA allosteric (dimerization) domain; This is the C-terminal regulatory (R) domain of alpha-isopropylmalate synthase, which catalyzes the first committed step in the leucine biosynthetic pathway. This domain, is an internally duplicated structure with a novel fold. It comprises two similar units that are arranged such that the two -helices pack together in the centre, crossing at an angle of 34 degrees, sandwiched between the two three-stranded, antiparallel beta-sheets. The overall domain is thus constructed as a beta-alpha-beta three-layer sandwich.
Pssm-ID: 400689 [Multi-domain] Cd Length: 112 Bit Score: 114.19 E-value: 2.01e-30
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy ...
5-263
4.65e-26
4-hydroxy-2-oxovalerate aldolase, N-terminal catalytic TIM barrel domain; 4-hydroxy 2-ketovalerate aldolase (Also known as 4-hydroxy-2-ketovalerate aldolase and 4-hydroxy-2-oxopentanoate aldolase (HOA)) converts 4-hydroxy-2-oxopentanoate to acetaldehyde and pyruvate, the penultimate step in the meta-cleavage pathway for the degradation of phenols, cresols and catechol. This family includes the Escherichia coli MhpE aldolase, the Pseudomonas DmpG aldolase, and the Burkholderia xenovorans BphI pyruvate aldolase. In Pseudomonas, the DmpG aldolase tightly associates with a dehydrogenase (DmpF ) and is inactive without it. HOA has a canonical TIM-barrel fold with a C-terminal extension that forms a funnel leading to the active site. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163681 Cd Length: 263 Bit Score: 106.81 E-value: 4.65e-26
Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; ...
5-260
5.12e-25
Clostridium kluyveri Re-citrate synthase and related proteins, catalytic TIM barrel domain; Re-citrate synthase (Re-CS) is a Clostridium kluyveri enzyme that converts acetyl-CoA and oxaloacetate to citrate. In most organisms, this reaction is catalyzed by Si-citrate synthase which is Si-face stereospecific with respect to C-2 of oxaloacetate, and phylogenetically unrelated to Re-citrate synthase. Re-citrate synthase is also found in a few other strictly anaerobic organisms. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163684 Cd Length: 279 Bit Score: 104.33 E-value: 5.12e-25
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; ...
7-276
7.14e-22
3-hydroxy-3-methylglutaryl-CoA lyase, catalytic TIM barrel domain; 3-hydroxy-3-methylglutaryl-CoA lyase (HMGL) catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate, one of the terminal steps in ketone body generation and leucine degradation, and is a key enzyme in the pathway that supplies metabolic fuel to extrahepatic tissues. Mutations in HMGL cause a human autosomal recessive disorder called primary metabolic aciduria that affects ketogenesis and leucine catabolism and can be fatal due to an inability to tolerate hypoglycemia. HMGL has a TIM barrel domain with a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. The cleavage of HMG-CoA requires the presence of a divalent cation like Mg2+ or Mn2+, and the reaction is thought to involve general acid/base catalysis. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163676 Cd Length: 274 Bit Score: 95.15 E-value: 7.14e-22
4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of ...
7-255
2.58e-11
4-hydroxy-2-oxovalerate aldolase-like, N-terminal catalytic TIM barrel domain; This family of bacterial enzymes is sequence-similar to 4-hydroxy-2-oxovalerate aldolase (HOA) but its exact function is unknown. This family includes the Bacteroides vulgatus Bvu_2661 protein and belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163682 Cd Length: 266 Bit Score: 64.12 E-value: 2.58e-11
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes ...
147-263
2.47e-04
Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain; This family includes the carboxyltransferase domains of pyruvate carboxylase (PC) and the transcarboxylase (TC) 5S subunit. Transcarboxylase 5S is a cobalt-dependent metalloenzyme subunit of the biotin-dependent transcarboxylase multienzyme complex. Transcarboxylase 5S transfers carbon dioxide from the 1.3S biotin to pyruvate in the second of two carboxylation reactions catalyzed by TC. The first reaction involves the transfer of carbon dioxide from methylmalonyl-CoA to the 1.3S biotin, and is catalyzed by the 12S subunit. These two steps allow a carboxylate group to be transferred from oxaloacetate to propionyl-CoA to yield pyruvate and methylmalonyl-CoA. The catalytic domain of transcarboxylase 5S has a canonical TIM-barrel fold with a large C-terminal extension that forms a funnel leading to the active site. Transcarboxylase 5S forms a homodimer and there are six dimers per complex. In addition to the catalytic domain, transcarboxylase 5S has several other domains including a carbamoyl-phosphate synthase domain, a biotin carboxylase domain, a carboxyltransferase domain, and an ATP-grasp domain. Pyruvate carboxylase, like TC, is a biotin-dependent enzyme that catalyzes the carboxylation of pyruvate to produce oxaloacetate. In mammals, PC has critical roles in gluconeogenesis, lipogenesis, glyceroneogenesis, and insulin secretion. Inherited PC deficiencies are linked to serious diseases in humans such as lactic acidemia, hypoglycemia, psychomotor retardation, and death. PC is a single-chain enzyme and is active only in its homotetrameric form. PC has three domains, an N-terminal biotin carboxylase domain, a carboxyltransferase domain (this alignment model), and a C-terminal biotin-carboxyl carrier protein domain. This family belongs to the DRE-TIM metallolyase superfamily. DRE-TIM metallolyases include 2-isopropylmalate synthase (IPMS), alpha-isopropylmalate synthase (LeuA), 3-hydroxy-3-methylglutaryl-CoA lyase, homocitrate synthase, citramalate synthase, 4-hydroxy-2-oxovalerate aldolase, re-citrate synthase, transcarboxylase 5S, pyruvate carboxylase, AksA, and FrbC. These members all share a conserved triose-phosphate isomerase (TIM) barrel domain consisting of a core beta(8)-alpha(8) motif with the eight parallel beta strands forming an enclosed barrel surrounded by eight alpha helices. The domain has a catalytic center containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".
Pssm-ID: 163675 Cd Length: 275 Bit Score: 42.80 E-value: 2.47e-04
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.
of the residues that compose this conserved feature have been mapped to the query sequence.
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