1mb4

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1mb4, resolution 1.84Å

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Crystal structure of aspartate semialdehyde dehydrogenase from vibrio cholerae with NADP and S-methyl-l-cysteine sulfoxide

Overview

L-Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes the, reductive dephosphorylation of beta-aspartyl phosphate to, L-aspartate-beta-semialdehyde in the aspartate biosynthetic pathway of, plants and micro-organisms. The aspartate pathway produces fully, one-quarter of the naturally occurring amino acids, but is not found in, humans or other eukaryotic organisms, making ASADH an attractive target, for the development of new antibacterial, fungicidal, or herbicidal, compounds. We have determined the structure of ASADH from Vibrio cholerae, in two states; the apoenzyme and a complex with NADP, and a covalently, bound active site inhibitor, S-methyl-L-cysteine sulfoxide. Upon binding, the inhibitor undergoes an enzyme-catalyzed reductive demethylation, leading to a covalently bound cysteine that is observed in the complex, structure. The enzyme is a functional homodimer, with extensive, intersubunit contacts and a symmetrical 4-amino acid bridge linking the, active site residues in adjacent subunits that could serve as a, communication channel. The active site is essentially preformed, with, minimal differences in active site conformation in the apoenzyme relative, to the ternary inhibitor complex. The conformational changes that do occur, result primarily from NADP binding, and are localized to the repositioning, of two surface loops located on the rim at opposite sides of the NADP, cleft.

About this Structure

1MB4 is a Single protein structure of sequence from Vibrio cholerae with CYS and NDP as ligands. Active as Aspartate-semialdehyde dehydrogenase, with EC number 1.2.1.11 Full crystallographic information is available from OCA.

Reference

A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae., Blanco J, Moore RA, Kabaleeswaran V, Viola RE, Protein Sci. 2003 Jan;12(1):27-33. PMID:12493825

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