| Primary Identifier | IPR036793 | Type | Homologous_superfamily |
| Short Name | Asp_carbatrfase_reg_N_sf |
| description | Aspartate carbamoyltransferase (aspartate transcarbamylase, ATCase) is an allosteric enzyme that plays a central role in the regulation of the pyrimidine pathway in bacteria. The holoenzyme is a dodecamer composed of six catalytic chains, each with an active site, and six regulatory chains lacking catalytic activity []. The catalytic subunits exist as a dimer of catalytic trimers, (c3)2, while the regulatory subunits exist as a trimer of regulatory dimers, (r2)3, therefore the complete holoenzyme can be represented as (c3)2(r2)3. The association of the catalytic subunits c3 with the regulatory subunits r2 is responsible for the establishment of positive co-operativity between catalytic sites for the binding of aspartate and it dictates the pattern of allosteric response toward nucleotide effectors. ATCase from Escherichia coli is the most extensively studied allosteric enzyme []. The crystal structure of the T-state, the T-state with CTP bound, the R-state with N-phosphonacetyl-L-aspartate (PALA) bound, and the R-state with phosphonoacetamide plus malonate bound have been used in interpreting kinetic and mutational studies.A high-resolution structure of E. coli ATCase in the presence of PALA (a bisubstrate analog) allows a detailed description of the binding at the active site of the enzyme and allows a detailed model of the tetrahedral intermediate to be constructed. The entire regulatory chain has been traced showing that the N-terminal regions of the regulatory chains R1 and R6 are located in close proximity to each other and to the regulatory site. This portion of the molecule may be involved in the observed asymmetry between the regulatory binding sites as well as in the heterotropic response of the enzyme []. The C-terminal domain of the regulatory chains have a rubredoxin-like zinc-bound fold. ATCase from Enterobacter agglomerans (Erwinia herbicola) (Pantoea agglomerans) differs from the other investigated enterobacterial ATCases by its absence of homotropic co-operativity toward the substrate aspartate and its lack of response to ATP which is an allosteric effector (activator) of this family of enzymes. Nevertheless, the E. herbicola ATCase has the same quaternary structure, two trimers of catalytic chains with three dimers of regulatory chains, (c3)2(r2)3, as other enterobacterial ATCases and shows extensive primary structure conservation []. This entry represents the N-terminal domain superfamily. Structurally, this domain has a ferredoxin-like fold, which consists of an alpha+beta sandwich with antiparallel β-sheet. |
