How sugars pucker: Electronic structure calculations map the kinetic landscape of fivebiologically paramount monosaccharides and their implications for enzymatic catalysis

Heather B. Mayes, Linda J. Broadbelt, Gregg T. Beckham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Glycoside hydrolases (GHs) distort carbohydrate ring geometry along particular "catalytic itineraries" during the cleavage of glycosidic bonds, illustrating the relationship between substrate conformation and reactivity. Previous theoretical studies of thermodynamics of isolated monosaccharides offer insights into the catalytic itineraries of particular sugars. However, kinetic accessibility of carbohydrate puckering conformations and the role of exocyclic groups have not yet been thoroughly addressed. Here we present the first complete library of low-energy local minima and puckering interconversion transition states for five biologically relevant pyranose sugars: β-xylose, β-mannose, α-glucose, β-glucose, and β-N-acetylglucosamine. These were obtained by a thorough theoretical investigation each of the 38 IUPAC designated puckering geometries and all possible conformations of the exocyclic groups. These calculations demonstrate that exocyclic groups must be explicitly considered when examining these interconversion pathways. Furthermore, these data enable evaluation of previous hypotheses of why enzymes perturb ring geometries from the low-energy equatorial chair (4C1) conformation. They show that the relative thermodynamics alone do not universally correlate with GH catalytic itineraries. For some sugars, particular puckers offer both catalytically favorable electronic structure properties, such as anomeric carbon partial charge, and low kinetic barriers to achieve a given puckering conformation. However, different factors correlate with catalytic itineraries for other sugars; for β-N-acetylglucosamine, the key N-acetyl arm confounds the puckering landscape and appears to be the crucial factor. Overall, this study reveals a more comprehensive understanding of why particular puckering geometries are favored in carbohydrate catalysis concomitant with the complexity of glycobiology.

Original languageEnglish (US)
Pages (from-to)1008-1022
Number of pages15
JournalJournal of the American Chemical Society
Volume136
Issue number3
DOIs
StatePublished - Jan 22 2014

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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