1MB4

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

Summary for 1MB4

• Entry DOI: 10.2210/pdb1mb4/pdb
• Related: 1GL3 1brm
• Descriptor: Aspartate-Semialdehyde Dehydrogenase, CYSTEINE, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• Functional Keywords: enzyme, aspartate-semialdehyde dehydrogenase, complex, vibrio cholerae, oxidoreductase
• Biological source: Vibrio cholerae
• Total number of polymer chains: 2
• Total formula weight: 82816.49

Authors

Blanco, J.,Moore, R.A.,Kabaleeswaran, V.,Viola, R.E. (deposition date: 2002-08-02, release date: 2003-01-07, Last modification date: 2023-12-13)

Primary citation

Blanco, J.,Moore, R.A.,Kabaleeswaran, V.,Viola, R.E.
A structural Basis for the Mechanism of Aspartate-beta-semialdehyde Dehydrogenase from Vibrio Cholerae
Protein Sci., 12:27-33, 2003

PubMed Abstract: 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.

PubMed: 12493825
DOI: 10.1110/ps.0230803

Experimental method

X-RAY DIFFRACTION (1.84 Å)