An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor

DOI: 10.1039/C7CC04977C

Authors: Tyson Belz (University of Melbourne) , Yi Jin (University of York) , Joan Coines (Universitat de Barcelona) , Carme Rovira (Universitat de Barcelona; Institució Catalana de Recerca i Estudis Avançats (ICREA)) , Gideon J. Davies (University of York) , Spencer J. Williams (University of Melbourne)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemical Communications , VOL 81

State: Published (Approved)
Published: July 2017
Diamond Proposal Number(s): 13587

Abstract: The non-hydrolyzable S-linked azasugars, 1,6-α-mannosylthio- and 1,6-α-mannobiosylthioisofagomine, were synthesized and shown to bind with high affinity to a family 76 endo-1,6-α-mannanase from Bacillus circulans. X-ray crystallography showed an atypical interaction of the isofagomine nitrogen with the catalytic acid/base. Molecular dynamics simulations reveal that the atypical binding results from sulfur perturbing the most stable form away from the nucleophile interaction preferred for the O-linked congener.

Diamond Keywords: Enzymes

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 03/08/2017 14:23

Documents:
C7CC04977C.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)