1gex
CRYSTAL STRUCTURE OF HISTIDINOL-PHOSPHATE AMINOTRANSFERASE COMPLEXED WITH HISTIDINOL-PHOSPHATE
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OverviewOverview
Histidinol-phosphate aminotransferase (HspAT) is a key enzyme on the, histidine biosynthetic pathway. HspAT catalyzes the transfer of the amino, group of L-histidinol phosphate (Hsp) to 2-oxoglutarate to form imidazole, acetol phosphate (IAP) and glutamate. Thus, HspAT recognizes two kinds of, substrates, Hsp and glutamate (double substrate recognition). The crystal, structures of native HspAT and its complexes with Hsp and, N-(5'-phosphopyridoxyl)-L-glutamate have been solved and refined to, R-factors of 19.7, 19.1, and 17.8% at 2.0, 2.2, and 2.3 A resolution, respectively. The enzyme is a homodimer, and the polypeptide chain of the, subunit is folded into one arm, one small domain, and one large domain., Aspartate aminotransferases (AspATs) from many species were classified, into aminotransferase subgroups Ia and Ib. The primary sequence of HspAT, is less than 18% identical to those of Escherichia coli AspAT of subgroup, Ia and Thermus thermophilus HB8 AspAT of subgroup Ib. The X-ray analysis, of HspAT showed that the overall structure is significantly similar to, that of AspAT of subgroup Ib rather than subgroup Ia, and the N-terminal, region moves close to the active site like that of subgroup Ib AspAT upon, binding of Hsp. The folding of the main-chain atoms in the active site is, conserved between HspAT and the AspATs, and more than 40% of the, active-site residues is also conserved. The eHspAT recognizes both Hsp and, glutamate by utilizing essentially the same active-site folding as that of, AspAT, conserving the essential residues for transamination reaction, and, replacing and relocating some of the active-site residues. The binding, sites for the phosphate and the alpha-carboxylate groups of the substrates, are roughly located at the same position and those for the imidazole and, gamma-carboxylate groups at the different positions. The mechanism for the, double substrate recognition observed in eHspAT is in contrast to that in, aromatic amino acid aminotransferase, where the recognition site for the, side chain of the acidic amino acid is formed at the same position as that, for the side chain of aromatic amino acids by large-scale rearrangements, of the hydrogen bond networks.
About this StructureAbout this Structure
1GEX is a Single protein structure of sequence from Escherichia coli with PLP and HSA as ligands. Active as Histidinol-phosphate transaminase, with EC number 2.6.1.9 Full crystallographic information is available from OCA.
ReferenceReference
Structures of Escherichia coli histidinol-phosphate aminotransferase and its complexes with histidinol-phosphate and N-(5'-phosphopyridoxyl)-L-glutamate: double substrate recognition of the enzyme., Haruyama K, Nakai T, Miyahara I, Hirotsu K, Mizuguchi H, Hayashi H, Kagamiyama H, Biochemistry. 2001 Apr 17;40(15):4633-44. PMID:11294630 [[Category: phosphoric acid mono-[2-amino-3-(3h-imidazol-4-yl)-propyl]ester]]
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