1gl3
ASPARTATE BETA-SEMIALDEHYDE DEHYDROGENASE IN COMPLEX WITH NADP AND SUBSTRATE ANALOGUE S-METHYL CYSTEINE SULFOXIDEASPARTATE BETA-SEMIALDEHYDE DEHYDROGENASE IN COMPLEX WITH NADP AND SUBSTRATE ANALOGUE S-METHYL CYSTEINE SULFOXIDE
Structural highlights
FunctionDHAS_ECOLI Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAspartate-beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the biosynthetic pathway through which bacteria, fungi, and the higher plants synthesize amino acids, including lysine and methionine and the cell wall component diaminopimelate from aspartate. Blocks in this biosynthetic pathway, which is absent in mammals, are lethal, and inhibitors of ASADH may therefore serve as useful antibacterial, fungicidal, or herbicidal agents. We have determined the structure of ASADH from Escherichia coli by crystallography in the presence of its coenzyme and a substrate analogue that acts as a covalent inhibitor. This structure is comparable to that of the covalent intermediate that forms during the reaction catalyzed by ASADH. The key catalytic residues are confirmed as cysteine 135, which is covalently linked to the intermediate during the reaction, and histidine 274, which acts as an acid/base catalyst. The substrate and coenzyme binding residues are also identified, and these active site residues are conserved throughout all of the ASADH sequences. Comparison of the previously determined apo-enzyme structure [Hadfield et al. J. Mol. Biol. (1999) 289, 991-1002] and the complex presented here reveals a conformational change that occurs on binding of NADP that creates a binding site for the amino acid substrate. These results provide a structural explanation for the preferred order of substrate binding that is observed kinetically. Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase.,Hadfield A, Shammas C, Kryger G, Ringe D, Petsko GA, Ouyang J, Viola RE Biochemistry. 2001 Dec 4;40(48):14475-83. PMID:11724560[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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