1PQU

Crystal Structure of the H277N Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae Bound with NADP, S-methyl cysteine sulfoxide and cacodylate

1PQU の概要

• エントリーDOI: 10.2210/pdb1pqu/pdb
• 関連するPDBエントリー: 1NWC 1NWH 1NX6 1PQP 1PR3 1PS8 1PU2
• 分子名称: Aspartate-semialdehyde dehydrogenase, CACODYLATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: enzyme, l-aspartate semialdehyde, cacodylate, nadp, oxidoreductase
• 由来する生物種: Haemophilus influenzae Rd
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 165501.57

構造登録者

Blanco, J.,Moore, R.A.,Viola, R.E. (登録日: 2003-06-19, 公開日: 2004-08-10, 最終更新日: 2024-11-20)

主引用文献

Blanco, J.,Moore, R.A.,Faehnle, C.R.,Coe, D.M.,Viola, R.E.
The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.
Acta Crystallogr.,Sect.D, 60:1388-1395, 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 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).

PubMed: 15272161
DOI: 10.1107/S0907444904012971

実験手法

X-RAY DIFFRACTION (1.92 Å)