1PQP

Crystal Structure of the C136S Mutant of Aspartate Semialdehyde Dehydrogenase from Haemophilus influenzae Bound with Aspartate Semialdehyde and Phosphate

1PQP の概要

• エントリーDOI: 10.2210/pdb1pqp/pdb
• 関連するPDBエントリー: 1NWC 1NWH 1NX6
• 分子名称: Aspartate-semialdehyde dehydrogenase, PHOSPHATE ION, L-HOMOSERINE, ... (4 entities in total)
• 機能のキーワード: enzyme, l-aspartate semialdehyde, l-aspartate semialdehyde dehydrogenase, phosphate, oxidoreductase
• 由来する生物種: Haemophilus influenzae Rd
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40781.76

構造登録者

Blanco, J.,Moore, R.A.,Faehnle, C.R.,Viola, R.E. (登録日: 2003-06-18, 公開日: 2004-08-10, 最終更新日: 2025-11-12)

主引用文献

Blanco, J.,Moore, R.A.,Faehnle, C.R.,Viola, R.E.
Critical catalytic functional groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.
Acta Crystallogr.,Sect.D, 60:1808-1815, 2004

PubMed Abstract: Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes the reductive dephosphorylation of beta-aspartyl phosphate to L-aspartate-beta-semialdehyde in the aspartate biosynthetic pathway. This pathway is not found in humans or other eukaryotic organisms, yet is required for the production of threonine, isoleucine, methionine and lysine in most microorganisms. The mechanism of this enzyme has been examined through the structures of two active-site mutants of ASADH from Haemophilus influenzae. Replacement of the enzyme active-site cysteine with serine (C136S) leads to a dramatic loss of catalytic activity caused by the expected decrease in nucleophilicity, but also by a change in the orientation of the serine hydroxyl group relative to the cysteine thiolate. In contrast, in the H277N active-site mutant the introduced amide is oriented in virtually the same position as that of the histidine imidazole ring. However, a shift in the position of the bound reaction intermediate to accommodate this shorter asparagine side chain, coupled with the inability of this introduced amide to serve as a proton acceptor, results in a 100-fold decrease in the catalytic efficiency of H277N relative to the native enzyme. These mutant enzymes have the same overall fold and high structural identity to native ASADH. However, small perturbations in the positioning of essential catalytic groups or reactive intermediates have dramatic effects on catalytic efficiency.

PubMed: 15388927
DOI: 10.1107/S0907444904020104

実験手法

X-RAY DIFFRACTION (2.06 Å)