Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5-phospho-d-arabinonhydrazide

FEBS Lett. 2018 May;592(10):1667-1680. doi: 10.1002/1873-3468.13059. Epub 2018 May 7.


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.

Keywords: Candida albicans; enzyme mechanism; inhibitor; phosphomannose isomerase; zinc metalloenzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / enzymology*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Hydrazines / chemistry*
  • Mannose-6-Phosphate Isomerase / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism
  • Substrate Specificity
  • Sugar Phosphates / chemistry*


  • 5-phospho-D-arabinonhydrazide
  • Hydrazines
  • Sugar Phosphates
  • Mannose-6-Phosphate Isomerase