1TA4

Crystal Structure Of Aspartate-Semialdehyde Dehydrogenase From Haemophilus Influenzae with a Bound Arsenate

Summary for 1TA4

• Entry DOI: 10.2210/pdb1ta4/pdb
• Related: 1NWC 1TB4
• Descriptor: Aspartate-semialdehyde dehydrogenase, ARSENATE (3 entities in total)
• Functional Keywords: aspartate-semialdehyde dehydrogenase, arsenate, aspartate biosynthetic pathway, haemophilus influenzae, oxidoreductase
• Biological source: Haemophilus influenzae
• Total number of polymer chains: 1
• Total formula weight: 40861.57

Authors

Viola, R.E. (deposition date: 2004-05-19, release date: 2004-12-07, Last modification date: 2024-02-14)

Primary citation

Faehnle, C.R.,Blanco, J.,Viola, R.E.
Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase.
Acta Crystallogr.,Sect.D, 60:2320-2324, 2004

PubMed 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.

PubMed: 15583380
DOI: 10.1107/S0907444904026411

Experimental method

X-RAY DIFFRACTION (2.28 Å)