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

Tyson Belz; Yi Jin; Joan Coines; Carme Rovira; Gideon J. Davies; Spencer J. Williams

doi:10.1039/C7CC04977C

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

Tyson Belz,^a Yi Jin,^b Joan Coines,^c Carme Rovira,

*^cd Gideon J. Davies

*^b and Spencer J. Williams

*^a

Author affiliations

* Corresponding authors

^a School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia
E-mail: sjwill@unimelb.edu.au

^b York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, UK
E-mail: gideon.davies@york.ac.uk

^c Departament de Química Inorgànica i Orgànica (Secció de Química Orgànica) & Institut de Química Teórica i Computacional (IQTCUB), Universitat de Barcelona, 08028 Barcelona, Spain
E-mail: c.rovira@ub.edu

^d Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain

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.

Supplementary files

Article information

DOI: https://doi.org/10.1039/C7CC04977C
Article type: Communication
Submitted: 28 Jun 2017
Accepted: 27 Jul 2017
First published: 28 Jul 2017
This article is Open Access

Download Citation

Chem. Commun., 2017,53, 9238-9241

Permissions

Request permissions

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

T. Belz, Y. Jin, J. Coines, C. Rovira, G. J. Davies and S. J. Williams, Chem. Commun., 2017, 53, 9238 DOI: 10.1039/C7CC04977C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Chemical Communications

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

Abstract

Supplementary files

Article information

Download Citation

Permissions

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

Social activity

Search articles by author

Spotlight

Advertisements