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Search results 1 to 18 out of 18 for Cad

Category restricted to ProteinDomain (x)

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Categories

Category: ProteinDomain
Type Details Score
Protein Domain
Type: Domain
Description: This entry represents the autophagy-related protein 2 CAD motif. The Atg2 protein, an integral membrane protein, is required for a range of functions including the regulation of autophagy in conjunction with the Atg1-Atg13 complex [, , ]. The precise function of this region, with its characteristic highly conserved CAD sequence motif, is not known.
Protein Domain
Type: Homologous_superfamily
Description: MmgE/PrpD superfamily members include 2-methylcitrate dehydratase (PrpD; ) and citrate/2-methylcitrate dehydratase MmgE. PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle []. This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an alpha beta domain []. Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus [].
Protein Domain
Type: Domain
Description: The CIDE-N or CAD domain is a ~78 amino acid protein-protein interaction domain in the N-terminal part of Cell death-Inducing DFF45-like Effector (CIDE) proteins, involved in apoptosis. At the final stage of programmed cell death, chromosomal DNA is degraded into fragments by Caspase-activated DNase (CAD), also named DNA fragmentation factor 40kDa (DFF40). In normal cells CAD/DFF40 is completely inhibited by its binding to DFF45 or Inhibitor of CAD (ICAD). Apoptotic stimuli provoke cleavage of ICAD/DFF45 by caspases, resulting in self-assembly of CAD/DFF40 into the active dimer [].Both CAD/DFF40 and ICAD/DFF45 possess an N-terminal CIDE-N domain that is involved in their interaction. The name of the CIDE-N domain refers to the CIDE proteins and CAD, where the domain forms the N-terminal part [, ]. The CIDE-N domains from different proteins can interact, e.g. CIDE-N of CIDE-B and ICAD/DFF45 with CIDE-N of CAD/DFF40, and such interactions can also be needed for proper folding [, ].Tertiary structures show that the CIDE-N domain forms an alpha/beta roll fold of five β-strands forming a single, mixed parallel/anti-parallel β-sheet with one []or two [, ]α-helices packed against the sheet. Binding surfaces of the CIDE-N domain form a central hydrophobic cluster, while specific binding interfaces can be formed by charged patches.Some proteins known to contain a CIDE-N domain include:Mammalian DNA fragmentation factor 40kDa (DFF40) or Caspase-activated deoxyribonuclease (CAD), an endonuclease that induces DNA fragmentation and chromatin condensation during apoptosis. The degradation of chromosomal DNA by CAD/DFF40 will kill the cells.Mammalian DNA fragmentation factor 45kDa (DFF45) or Inhibitor of CAD (ICAD), which controls the activity and proper folding of CAD/DFF40. Mammalian CIDE-A and CIDE-B, activators of cell death and DNA fragmentation that can be inhibited by ICAD/DFF45. In contrast with CAD and ICAD, the CIDE proteins are expressed in a highly restricted way and show pronounced tissue specificity.Fruit fly DNAation factor DREP1, a DFF45 homologue that can inhibit CIDE-A-induced apoptosis.
Protein Domain
Type: Family
Description: This entry represents proteins from the MmgE/PrpD family, which includes 2-methylcitrate dehydratase (PrpD; ). PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle []. This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an alpha+beta domain []. Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus []. Citrate/2-methylcitrate dehydratase from Bacillus subtilis is involved in the tricarboxylic acid (TCA) and methylcitric acid cycles as it has both 2-methylcitrate dehydratase and citrate dehydratase activities [].
Protein Domain
Type: Homologous_superfamily
Description: MmgE/PrpD superfamily members include 2-methylcitrate dehydratase (PrpD; ) and citrate/2-methylcitrate dehydratase MmgE. PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle []. This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an alpha beta domain []. Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus [].This superfamily represents the small domain found in PrpD.
Protein Domain
Type: Homologous_superfamily
Description: MmgE/PrpD superfamily members include 2-methylcitrate dehydratase (PrpD; ) and citrate/2-methylcitrate dehydratase MmgE. PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle []. This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an alpha beta domain []. Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family. CAD is essential for itaconic acid production in Aspergillus terreus [].This superfamily represents the large domain found in PrpD.
Protein Domain
Type: Domain
Description: CadC is an integral membrane protein of 512 amino acids comprising an N-terminal cytoplasmic DNA-binding domain, a transmembrane helix, and a C-terminal periplasmic domain. CadC belongs to the ToxR-like regulators that encompass biochemically non-modified one-component systems with similar gross topology, including several low pH-induced transcription regulators. Structural analysis of the C-terminal periplasmic domain indicates that it resembles the sensory domain of a (pH-activated) ToxR-like regulator. Furthermore, it is composed of two subdomains with a cavity at their interface that is suited to accommodate cadaverine, the feedback inhibitor of the Cad system. This is the N-terminal subdomain of the C-terminal periplasmic domain. It is composed of five-stranded β-sheets [].
Protein Domain
Type: Domain
Description: This entry represents the N-terminal domain of 2-methylcitrate dehydratase PrpD.PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle []. This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an α/β domain []. Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family []. CAD is essential for itaconic acid production in Aspergillus terreus []. Citrate/2-methylcitrate dehydratase from Bacillus subtilis is involved in the tricarboxylic acid (TCA) and methylcitric acid cycles as it has both 2-methylcitrate dehydratase and citrate dehydratase activities [].
Protein Domain
Type: Domain
Description: This entry represents the C-terminal domain of 2-methylcitrate dehydratase PrpD.PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle []. This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an α/β domain []. Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family []. CAD is essential for itaconic acid production in Aspergillus terreus []. Citrate/2-methylcitrate dehydratase from Bacillus subtilis is involved in the tricarboxylic acid (TCA) and methylcitric acid cycles as it has both 2-methylcitrate dehydratase and citrate dehydratase activities [].
Protein Domain
Type: Family
Description: This family contains two related enzymes:Aspartate carbamoyltransferase () (ATCase) catalyses the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the de novobiosynthesis of pyrimidine nucleotides []. In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals []) that also catalyses other steps of the biosynthesis of pyrimidines.Ornithine carbamoyltransferase () (OTCase) catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals, this enzyme participates in the urea cycle []and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine [](the arginine deaminase pathway).It has been shown []that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies [], to be implicated in binding the phosphoryl group of carbamoyl phosphate.
Protein Domain
Type: Family
Description: Dihydroorotase belongs to MEROPS peptidase family M38 (clan MJ), where it is classified as a non-peptidase homologue. DHOase catalyses the third step in the de novobiosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity [].In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In the metazoa, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila melanogaster and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis []. The DHOase domain is located in the central part of this polyprotein. In yeast, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain []is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.The comparison of DHOase sequences from various sources shows []that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested []to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold [].This family represents the homodimeric form of dihydroorotase . It is found in bacteria, plants and fungi; URA4 of yeast is a member of this group of sequences.
Protein Domain
Type: Homologous_superfamily
Description: This domain superfamily contains two related enzymes:Aspartate carbamoyltransferase () (ATCase) catalyses the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the de novobiosynthesis of pyrimidine nucleotides []. In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi-functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals []) that also catalyses other steps of the biosynthesis ofpyrimidines.Ornithine carbamoyltransferase () (OTCase) catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle []and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine [](the arginine deaminase pathway).It has been shown []that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies [], to be implicated in binding the phosphoryl group of carbamoyl phosphate.
Protein Domain
Type: Family
Description: Dihydroorotase belongs to MEROPS peptidase family M38 (clan MJ), and includes peptides classified as a non-peptidase homologues. DHOase catalyses the third step in the de novobiosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity [].In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC). In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila melanogaster and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis []. The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain []is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.The comparison of DHOase sequences from various sources shows []that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested []to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold [].Dihydroorotase 'multifunctional complex type' , in contrast to the homodimeric type of dihydroorotase found in Escherichia coli, tends to appear in a large multifunctional complex with aspartate transcarbamoylase. Homologous domains appear in multifunctional proteins of higher eukaryotes. In some species, including Pseudomonas putida and Pseudomonas aeruginosa, this protein is inactive but is required as a non-catalytic subunit of aspartate transcarbamoylase (ATCase). In these species, a second, active dihydroorotase is also present.
Protein Domain
Type: Conserved_site
Description: This group contains a number of protein families, example are:Archaeal and bacterial dihydroorotase () (DHOase)Allantoinase ()Dihydroorotase belongs to MEROPS peptidase family M38 (clan MJ), where it is classified as a non-peptidase homologue. DHOase catalyses the third step in the de novobiosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion which is required for its catalytic activity [].In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid residues (gene pyrC) []. In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila melanogaster and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis []. The DHOase domain is located in the central part of this polyprotein. In yeasts, DHOase is encoded by a monofunctional protein (gene URA4). However, a defective DHOase domain []is found in a multifunctional protein (gene URA2) that catalyzes the first two steps of pyrimidine biosynthesis.The comparison of DHOase sequences from various sources shows []that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested []to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold [].Allantoinase () is the enzyme that hydrolyzes allantoin into allantoate. In yeast (gene DAL1) [], it is the first enzyme in the allantoin degradation pathway; in amphibians []and fishs it catalyzes the second step in the degradation of uric acid. The sequence of allantoinase is evolutionary related to that of DHOases.
Protein Domain
Type: Domain
Description: Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine () or ammonia (), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates [, ]. CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate []. The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase () (ACC), propionyl-CoA carboxylase () (PCCase), pyruvate carboxylase () (PC) and urea carboxylase ().Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain []. CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites []. The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein []. The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP []. There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia []. CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains []. This entry represents the CPSase domain of the large subunit of carbamoyl phosphate synthase.
Protein Domain
Type: Family
Description: Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine () or ammonia (), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates [, ]. CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate []. The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase () (ACC), propionyl-CoA carboxylase () (PCCase), pyruvate carboxylase () (PC) and urea carboxylase ().Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain []. CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites []. The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein []. The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP []. There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia []. CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains []. This entry represents glutamine-dependent CPSase () from prokaryotes and eukaryotes (CPSase II).
Protein Domain
Type: Domain
Description: Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group []. The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified [, ]: class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). Class-I (or type 1) GATase domains have been found in the following enzymes:The second component of anthranilate synthase (AS) []. AS catalyzes the biosynthesis of anthranilate from chorismate and glutamine. AS is generally a dimeric enzyme: the first component can synthesize anthranilate using ammonia rather than glutamine, whereas component II provides the GATase activity []. In some bacteria and in fungi the GATase component of AS is part of a multifunctional protein that also catalyzes other steps of the biosynthesis of tryptophan.The second component of 4-amino-4-deoxychorismate (ADC) synthase, a dimeric prokaryotic enzyme that functions in the pathway that catalyzes the biosynthesis of para-aminobenzoate (PABA) from chorismate and glutamine. The second component (gene pabA) provides the GATase activity [].CTP synthase. CTP synthase catalyzes the final reaction in the biosynthesis of pyrimidine, the ATP-dependent formation of CTP from UTP and glutamine. CTP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the C-terminal section [].GMP synthase (glutamine-hydrolyzing). GMP synthase catalyzes the ATP-dependent formation of GMP from xanthosine 5'-phosphate and glutamine. GMP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the N-terminal section [, ].Glutamine-dependent carbamoyl-phosphate synthase (GD-CPSase); an enzyme involved in both arginine and pyrimidine biosynthesis and which catalyzes the ATP-dependent formation of carbamoyl phosphate from glutamine and carbon dioxide. In bacteria GD-CPSase is composed of two subunits: the large chain (gene carB) provides the CPSase activity, while the small chain (gene carA) provides the GATase activity. In yeast the enzyme involved in arginine biosynthesis is also composed of two subunits: CPA1 (GATase), and CPA2 (CPSase). In most eukaryotes, the first three steps of pyrimidine biosynthesis are catalyzed by a large multifunctional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals). The GATase domain is located at the N-terminal extremity of this polyprotein [].Phosphoribosylformylglycinamidine synthase, an enzyme that catalyzes the fourth step in the de novo biosynthesis of purines. In some species of bacteria and rchaea, FGAM synthase II is composed of two subunits: a small chain (gene purQ) which provides the GATase activity and a large chain (gene purL) which provides the aminator activity. In eukaryotes and Gram-negative bacteria a single polypeptide (large type of purL) contains a FGAM synthethase domain and the GATase as the C-terminal domain [].Imidazole glycerol phosphate synthase subunit hisH, an enzyme that catalyzes the fifth step in the biosynthesis of histidine.A triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity [, ]. Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.
Protein Domain
Type: Domain
Description: Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine () or ammonia (), and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates [, ]. CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate []. The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase () (ACC), propionyl-CoA carboxylase () (PCCase), pyruvate carboxylase () (PC) and urea carboxylase ().Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain []. CPSase heterodimers from Escherichia coli contain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites []. The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein []. The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP []. There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia []. CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains []. This entry represents the ATP-binding domain found in the large subunit of carbamoyl phosphate synthase, as well as in other proteins, including acetyl-CoA carboxylases and pyruvate carboxylases.