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

TY - JOUR

T1 - An atypical interaction explains the high-affinity of a non-hydrolyzable S-linked 1,6-α-mannanase inhibitor

AU - Belz, Tyson

AU - Jin, Yi

AU - Coines, Joan

AU - Rovira, Carme

AU - Davies, Gideon J.

AU - Williams, Spencer J.

N1 - ©The Royal Society of Chemistry 2017. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

PY - 2017/8/25

Y1 - 2017/8/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85027412762&partnerID=8YFLogxK

U2 - 10.1039/c7cc04977c

DO - 10.1039/c7cc04977c

M3 - Article

AN - SCOPUS:85027412762

SN - 1359-7345

VL - 53

SP - 9238

EP - 9241

JO - Chemical Communications

JF - Chemical Communications

IS - 66

ER -