4MLR

dihydrodipicolinate synthase from C. jejuni, Y110F mutation with pyruvate and Lysine

4MLR の概要

• エントリーDOI: 10.2210/pdb4mlr/pdb
• 関連するPDBエントリー: 4MLJ
• 分子名称: dihydrodipicolinate synthase, LYSINE, 1,2-ETHANEDIOL, ... (8 entities in total)
• 機能のキーワード: schiff-base, aldolase, tim barrel, lyase
• 由来する生物種: campylobacter jejuni
• 細胞内の位置: Cytoplasm : Q9PPB4
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 273091.83

構造登録者

Conly, C.J.T. (登録日: 2013-09-06, 公開日: 2015-01-14, 最終更新日: 2023-11-29)

主引用文献

Conly, C.J.,Skovpen, Y.V.,Li, S.,Palmer, D.R.,Sanders, D.A.
Tyrosine 110 Plays a Critical Role in Regulating the Allosteric Inhibition of Campylobacter jejuni Dihydrodipicolinate Synthase by Lysine.
Biochemistry, 53:7396-7406, 2014

PubMed Abstract: Dihydrodipicolinate synthase (DHDPS), an enzyme found in most bacteria and plants, controls a critical step in the biosynthesis of l-lysine and meso-diaminopimelate, necessary components for bacterial cell wall biosynthesis. DHDPS catalyzes the condensation of pyruvate and (S)-aspartate-β-semialdehyde, forming an unstable product that is dehydrated to dihydrodipicolinate. The tetrameric enzyme is allosterically inhibited by l-lysine, and a better understanding of the allosteric inhibition mechanism is necessary for the design of potent antibacterial therapeutics. Here we describe the high-resolution crystal structures of DHDPS from Campylobacter jejuni with and without its inhibitor bound to the allosteric sites. These structures reveal a role for Y110 in the regulation of the allosteric inhibition by lysine. Mutation of Y110 to phenylalanine results in insensitivity to lysine inhibition, although the mutant crystal structure reveals that lysine does bind in the allosteric site. Comparison of the lysine-bound Y110F structure with wild-type structures reveals that key structural changes due to lysine binding are absent in this mutant.

PubMed: 25369463
DOI: 10.1021/bi5012157

実験手法

X-RAY DIFFRACTION (2.2 Å)