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Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5‐phospho‐ d ‐arabinonhydrazide
Author(s) -
Ahmad Lama,
Plancqueel Stéphane,
Dubosclard Virginie,
Lazar Noureddine,
Ghattas Wadih,
Li de la SierraGallay Inès,
Tilbeurgh Herman,
Salmon Laurent
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13059
Subject(s) - isomerase , chemistry , isomerization , stereochemistry , substrate (aquarium) , prolyl isomerase , candida albicans , catalysis , enzyme , biochemistry , biology , microbiology and biotechnology , ecology , pin1
Type I phosphomannose isomerases ( PMI s) are zinc‐dependent monofunctional metalloenzymes catalysing the reversible isomerization of d ‐mannose 6‐phosphate to d ‐fructose 6‐phosphate. 5‐Phospho‐ d ‐arabinonhydrazide (5 PAH z), designed as an analogue of the enediolate high‐energy intermediate, strongly inhibits PMI from Candida albicans (Ca PMI ). In this study, we report the 3D crystal structure of Ca PMI complexed with 5 PAH z 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 PMI s. A detailed mechanism of the reversible isomerization is proposed.