BROWSE

Related Researcher

Author

Hong, Sung You
Synthetic Organic Chemistry Laboratory
Research Interests
  • Synthetic organic chemistry, transition metals, oxidation state

ITEM VIEW & DOWNLOAD

Mechanistic evidence for a front-side, S(N)i-type reaction in a retaining glycosyltransferase

Cited 47 times inthomson ciCited 41 times inthomson ci
Title
Mechanistic evidence for a front-side, S(N)i-type reaction in a retaining glycosyltransferase
Author
Lee, Seung SeoHong, Sung YouErrey, James C.Izumi, AtsushiDavies, Gideon J.Davis, Benjamin G.
Keywords
SUBSTRATE-ASSISTED CATALYSIS; ENZYMATIC GLYCOSYL TRANSFER; TRANSITION-STATE; ALPHA-GALACTOSYLTRANSFERASE; TREHALOSE PHOSPHORYLASE; NEISSERIA-MENINGITIDIS; SCHIZOPHYLLUM-COMMUNE; COVALENT INTERMEDIATE; GLUCOSYL TRANSFER; ACTIVE-SITE
Issue Date
201109
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE CHEMICAL BIOLOGY, v.7, no.9, pp.631 - 638
Abstract
A previously determined crystal structure of the ternary complex of trehalose-6-phosphate synthase identified a putative transition state-like arrangement based on validoxylamine A 6'-O-phosphate and uridine diphosphate in the active site. Here linear free energy relationships confirm that these inhibitors are synergistic transition state mimics, supporting front-face nucleophilic attack involving hydrogen bonding between leaving group and nucleophile. Kinetic isotope effects indicate a highly dissociative oxocarbenium ion-like transition state. Leaving group O-18 effects identified isotopically sensitive bond cleavages and support the existence of a hydrogen bond between the nucleophile and departing group. Bronsted analysis of nucleophiles and Taft analysis highlight participation of the nucleophile in the transition state, also consistent with a front-face mechanism. Together, these comprehensive, quantitative data substantiate this unusual enzymatic reaction mechanism. Its discovery should prompt useful reassessment of many biocatalysts and their substrates and inhibitors.
URI
Go to Link
DOI
http://dx.doi.org/10.1038/NCHEMBIO.628
ISSN
1552-4450
Appears in Collections:
ECHE_Journal Papers

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qr_code

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU