2qb3
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Structural Studies Reveal the Inactivation of E. coli L-Aspartate Aminotransferase by (s)-4,5-dihydro-2-thiophenecarboxylic acid (SADTA) via Two Mechanisms (at pH 7.5)
OverviewOverview
As a mechanism-based inactivator of PLP-enzymes, (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid (SADTA) was, cocrystallized with Escherichia coli aspartate aminotransferase (l-AspAT), at a series of pH values ranging from 6 to 8. Five structural models with, high resolution (1.4-1.85 A) were obtained for l-AspAT-SADTA complexes at, pH 6.0, 6.5, 7.0, 7.5, and 8.0. Electron densities of the models showed, that two different adducts had formed in the active sites. One adduct was, formed from SADTA covalently linked to pyridoxal 5'-phosphate (PLP) while, the other adduct was formed with the inhibitor covalently linked to, Lysine246,1 the active site lysine. Moreover, there is a strong indication, based on the electron densities that the occurrence of the two adducts is, pH dependent. We conclude that SADTA inactivates l-AspAT via two different, mechanisms based on the binding direction of the inactivator., Additionally, the structural models also show pH dependence of the protein, structure itself, which provided detailed mechanistic implications for, l-AspAT.
About this StructureAbout this Structure
2QB3 is a Single protein structure of sequence from Escherichia coli with , , and as ligands. Active as Aspartate transaminase, with EC number 2.6.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Inactivation of Escherichia coli l-Aspartate Aminotransferase by (S)-4-Amino-4,5-dihydro-2-thiophenecarboxylic Acid Reveals "A Tale of Two Mechanisms"(,)., Liu D, Pozharski E, Lepore BW, Fu M, Silverman RB, Petsko GA, Ringe D, Biochemistry. 2007 Aug 22;. PMID:17713924
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