5NW7

Crystal structure of candida albicans phosphomannose isomerase in complex with inhibitor

5NW7 の概要

• エントリーDOI: 10.2210/pdb5nw7/pdb
• 分子名称: Mannose-6-phosphate isomerase, ZINC ION, [(2~{R},3~{R},4~{S})-5-diazanyl-2,3,4-tris(oxidanyl)-5-oxidanylidene-pentyl] dihydrogen phosphate, ... (4 entities in total)
• 機能のキーワード: aldose-ketose isomerase, isomerase, complex inhibitor
• 由来する生物種: Candida albicans (Yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50854.71

構造登録者

Li de la Sierra-Gallay, I.,Ahmad, L.,Plancqueel, S.,van Tilbeurgh, H.,Salmon, L. (登録日: 2017-05-05, 公開日: 2018-05-02, 最終更新日: 2024-01-17)

主引用文献

Ahmad, L.,Plancqueel, S.,Dubosclard, V.,Lazar, N.,Ghattas, W.,Li de la Sierra-Gallay, I.,van Tilbeurgh, H.,Salmon, L.
Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5-phospho-d-arabinonhydrazide.
FEBS Lett., 592:1667-1680, 2018

PubMed Abstract: Type I phosphomannose isomerases (PMIs) are zinc-dependent monofunctional metalloenzymes catalysing the reversible isomerization of d-mannose 6-phosphate to d-fructose 6-phosphate. 5-Phospho-d-arabinonhydrazide (5PAHz), designed as an analogue of the enediolate high-energy intermediate, strongly inhibits PMI from Candida albicans (CaPMI). In this study, we report the 3D crystal structure of CaPMI complexed with 5PAHz at 1.85 Å resolution. The high-resolution structure suggests that Glu294 is the catalytic base that transfers a proton between the C1 and C2 carbon atoms of the substrate. Bidentate coordination of the inhibitor explains the stereochemistry of the isomerase activity, as well as the absence of both anomerase and C2-epimerase activities for Type I PMIs. A detailed mechanism of the reversible isomerization is proposed.

PubMed: 29687459
DOI: 10.1002/1873-3468.13059

実験手法

X-RAY DIFFRACTION (1.85 Å)