PDBsum entry: 1mc4

Oxidoreductase

PDB id: 1mc4

Contents

Protein chain

369 a.a. *

Waters ×44

* Residue conservation analysis

PDB id:

1mc4

Name:

Oxidoreductase

Title:

Crystal structure of aspartate-semialdehyde dehydrogenase fr cholerae el tor

Structure:

Aspartate-semialdehyde dehydrogenase. Chain: a. Engineered: yes

Source:

Vibrio cholerae. Organism_taxid: 666. Gene: asd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.77Å R-factor: 0.215 R-free: 0.281

Authors:

J.Blanco,R.A.Moore,V.Kabaleeswaran,R.E.Viola

Key ref:

J.Blanco et al. (2003). A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae. Protein Sci, 12, 27-33. PubMed id: 12493825 DOI: 10.1110/ps.0230803

Date:

05-Aug-02 Release date: 18-Mar-03

Protein chain

Q9KQG2  (Q9KQG2_VIBCH) -  Aspartate-semialdehyde dehydrogenase 1

Seq: 370 a.a.

Struc: 369 a.a.

Enzyme reactions

• Enzyme class: E.C.1.2.1.11 - Aspartate-semialdehyde dehydrogenase.
• Pathway: Lysine biosynthesis (early stages)
• Reaction: L-aspartate 4-semialdehyde + phosphate + NADP⁺ = L-4-aspartyl phosphate + NADPH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: oxidation-reduction process (9 terms)
• Biochemical function: nucleotide binding (8 terms)

reference

DOI no: 10.1110/ps.0230803

Protein Sci 12:27-33 (2003)

PubMed id: 12493825

A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae.

J.Blanco, R.A.Moore, V.Kabaleeswaran, R.E.Viola.

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.

Selected figure(s)

Figure 1.
Figure 1. Ribbon diagram of V. cholerae ASADH dimer with NADP and SMCS bound. The N-terminal domains are shown in darker blue and orange. The central C-terminal domains are shown in red and light blue. Drawings were rendered with Molscript and Raster3D.

Figure 5.
Figure 5. (A) The active sites in the dimer are interconnected through a -stacking interactions and hydrogen bonds. One active site is in the open conformation and the other is closed as shown by the different Pro192 to NADP distances. NADP is shown as a spacefilling model. (B) Diagram of residues involved in the pathway that is proposed to allow communication between the active sites, with the bound inhibitor SMCS shown in lighter shading.

The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 27-33) copyright 2003.

Figures were selected by the author.