5NW7

Crystal structure of candida albicans phosphomannose isomerase in complex with inhibitor

Summary for 5NW7

• Entry DOI: 10.2210/pdb5nw7/pdb
• Descriptor: 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)
• Functional Keywords: aldose-ketose isomerase, isomerase, complex inhibitor
• Biological source: Candida albicans (Yeast)
• Total number of polymer chains: 1
• Total formula weight: 50854.71

Authors

Li de la Sierra-Gallay, I.,Ahmad, L.,Plancqueel, S.,van Tilbeurgh, H.,Salmon, L. (deposition date: 2017-05-05, release date: 2018-05-02, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)