Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5‐phospho‐d‐arabinonhydrazide. Issue 10 (7th May 2018)

• Record Type: Journal Article
• Authors: Ahmad, Lama; Plancqueel, Stéphane; Dubosclard, Virginie; Lazar, Noureddine; Ghattas, Wadih; Li de la Sierra‐Gallay, Inès; van Tilbeurgh, Herman; Salmon, Laurent
• Is Part Of: FEBS letters. Volume 592:Issue 10(2018)
• Page Start: 1667
• Page End: 1680
• Publication Date: 2018-05-07
• Subjects: Candida albicans -- enzyme mechanism -- inhibitor -- phosphomannose isomerase -- zinc metalloenzyme; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13059
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Type I phosphomannose isomerases (PMIs) are zinc‐dependent monofunctional metalloenzymes catalysing the reversible isomerization ofd ‐mannose 6‐phosphate tod ‐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. Abstract :