PDBsum entry: 1tb4

Oxidoreductase

PDB id: 1tb4

Contents

Protein chain

357 a.a. *

Ligands

PEJ

Waters ×112

* Residue conservation analysis

PDB id:

1tb4

Name:

Oxidoreductase

Title:

Crystal structure of aspartate-semialdehyde dehydrogenase fr haemophilus influenzae with a bound periodate

Structure:

Aspartate-semialdehyde dehydrogenase. Chain: a. Synonym: asa dehydrogenase, asadh. Engineered: yes

Source:

Haemophilus influenzae. Organism_taxid: 727. Gene: asd, hi0646. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.15Å R-factor: 0.230 R-free: 0.288

Authors:

R.E.Viola

Key ref:

C.R.Faehnle et al. (2004). Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase. Acta Crystallogr D Biol Crystallogr, 60, 2320-2324. PubMed id: 15583380 DOI: 10.1107/S0907444904026411

Date:

19-May-04 Release date: 07-Dec-04

Protein chain

P44801  (DHAS_HAEIN) -  Aspartate-semialdehyde dehydrogenase

Seq: 371 a.a.

Struc: 357 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: 10.1107/S0907444904026411

Acta Crystallogr D Biol Crystallogr 60:2320-2324 (2004)

PubMed id: 15583380

Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase.

C.R.Faehnle, J.Blanco, R.E.Viola.

ABSTRACT

The reversible dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta-semialdehyde (ASA) in the aspartate biosynthetic pathway is catalyzed by aspartate-beta-semialdehyde dehydrogenase (ASADH). The phosphate that is present to activate the aspartate carboxyl group is held in a separate and distinct binding site once removed and prior to its release from the enzyme. This site had been shown to be selective for tetrahedral oxyanions, with several competitive inhibitors and alternative substrates previously identified for the reverse reaction. Structural studies have now shown that the most potent oxyanion inhibitor (periodate) and a good alternative substrate (arsenate) each occupy the same catalytic phosphate-binding site. However, a rotation of a threonine side chain (Thr137) in the periodate complex disrupts an important hydrogen-bonding interaction with an active-site glutamate (Glu243) that participates in substrate orientation. This subtle change appears to be the difference between a substrate and an inhibitor of this enzyme.

Selected figure(s)

Figure 1.
Figure 1 An abbreviated mechanism of the reaction catalyzed by aspartate -semialdehyde dehydrogenase in the reverse (non-physiological) direction.

Figure 4.
Figure 4 Stereoview of an overlay of H. influenzae ASA-phosphate structure (blue) and the periodate-bound structure (green). Periodate binding at only the catalytic site results in a reorientation of Thr137 that disrupts the hydrogen bond to an important substrate-orienting group (Glu243). Ser139 is repositioned in the periodate structure and forms a new hydrogen-bonding interaction with the backbone carbonyl of the active-site nucleophile (Cys136).

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2004, 60, 2320-2324) copyright 2004.

Figures were selected by an automated process.