1gl3: Difference between revisions
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==Overview== | ==Overview== | ||
Aspartate-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, ... | Aspartate-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. | ||
==About this Structure== | ==About this Structure== | ||
1GL3 is a | 1GL3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with CYS and NDP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aspartate-semialdehyde_dehydrogenase Aspartate-semialdehyde dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.11 1.2.1.11] Structure known Active Site: AT1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GL3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
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Revision as of 15:57, 5 November 2007
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ASPARTATE BETA-SEMIALDEHYDE DEHYDROGENASE IN COMPLEX WITH NADP AND SUBSTRATE ANALOGUE S-METHYL CYSTEINE SULFOXIDE
OverviewOverview
Aspartate-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.
About this StructureAbout this Structure
1GL3 is a Single protein structure of sequence from Escherichia coli with CYS and NDP as ligands. Active as Aspartate-semialdehyde dehydrogenase, with EC number 1.2.1.11 Structure known Active Site: AT1. Full crystallographic information is available from OCA.
ReferenceReference
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
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