1PQP: Crystal Structure Of The C136s Mutant Of Aspartate Semialdehyde Dehydrogenase From Haemophilus Influenzae Bound With Aspartate Semialdehyde And Phosphate

Citation:
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 product of this reaction is a key intermediate in the biosynthesis of diaminopimelic acid, an integral component of bacterial cell walls and a metabolic precursor of lysine and also a precursor in the biosynthesis of threonine, isoleucine and methionine. The structures of selected Haemophilus influenzae ASADH mutants were determined in order to evaluate the residues that are proposed to interact with the substrates ASA or phosphate. The substrate Km values are not altered by replacement of either an active-site arginine (Arg270) with a lysine or a putative phosphate-binding group (Lys246) with an arginine. However, the interaction of phosphate with the enzyme is adversely affected by replacement of Arg103 with lysine and is significantly altered when a neutral leucine is substituted at this position. A conservative Glu243 to aspartate mutant does not alter either ASA or phosphate binding, but instead results in an eightfold increase in the Km for the coenzyme NADP. Each of the mutations is shown to cause specific subtle active-site structural alterations and each of these changes results in decreases in catalytic efficiency ranging from significant (approximately 3% native activity) to substantial (<0.1% native activity).
PDB ID: 1PQPDownload
MMDB ID: 28868
PDB Deposition Date: 2003/6/18
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.06  Å
Source Organism:
Similar Structures:
Biological Unit for 1PQP: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1PQP
Label Count Molecule
Proteins (2 molecules)
2
Aspartate-semialdehyde Dehydrogenase(Gene symbol: asd)
Molecule annotation
Chemicals (4 molecules)
1
2
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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