Glucosyl epi-cyclophellitol allows mechanism-based inactivation and structural analysis of human pancreatic α-amylase.

Abstract:

:As part of a search for selective, mechanism-based covalent inhibitors of human pancreatic α-amylase we describe the chemoenzymatic synthesis of the disaccharide analog α-glucosyl epi-cyclophellitol, demonstrate its stoichiometric reaction with human pancreatic α-amylase and evaluate the time dependence of its inhibition. X-ray crystallographic analysis of the covalent derivative so formed confirms its reaction at the active site with formation of a covalent bond to the catalytic nucleophile D197. The structure illuminates the interactions with the active site and confirms OH4' on the nonreducing end sugar as a good site for attachment of fluorescent tags in generating probes for localization and quantitation of amylase in vivo.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Caner S,Zhang X,Jiang J,Chen HM,Nguyen NT,Overkleeft H,Brayer GD,Withers SG

doi

10.1002/1873-3468.12143

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

1143-51

issue

8

eissn

0014-5793

issn

1873-3468

journal_volume

590

pub_type

信件
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