Journal article

A Single Glycosidase Harnesses Different Pyranoside Ring Transition State Conformations for Hydrolysis of Mannosides and Glucosides

A Tankrathok, J Iglesias-Fernández, RJ Williams, S Pengthaisong, S Baiya, Z Hakki, RC Robinson, M Hrmova, C Rovira, SJ Williams, JR Ketudat Cairns

ACS Catalysis | Published : 2015

Abstract

Hydrolysis of β-d-mannosides by β-mannosidases typically proceeds via a B2,5 transition state conformation for the pyranoside ring, while that of β-d-glucosides by β-glucosidases proceeds through a distinct 4H3 transition state conformation. However, rice Os7BGlu26 β-glycosidase hydrolyzes 4-nitrophenyl β-d-glucoside and β-d-mannoside with similar efficiencies. The origin of this dual substrate specificity was investigated by kinetic, structural, and computational approaches. The glycosidase inhibitors glucoimidazole and mannoimidazole inhibited Os7BGlu26 with Ki values of 2.7 nM and 10.4 μM, respectively. In X-ray crystal structures of complexes with Os7BGlu26, glucoimidazole bound to the a..

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University of Melbourne Researchers

Grants

Awarded by Thailand Research Fund


Awarded by Generalitat de Catalunya


Awarded by Spanish Ministry of Economy and Competitiveness


Awarded by Royal Golden Jubilee Ph.D. Scholarship from Thailand Research Fund


Funding Acknowledgements

We thank Giovanni Bussi and Alejandro Ley for help in implementing the puckering coordinates for six-membered rings as collective variables in Plumed2. This work was supported by the Thailand Research Fund Grant BRG5680012, the Strategic Scholarships for Frontier Research Network Ph.D. Program, the National Research University Project to Suranaree University of Technology from the Commission on Higher Education of Thailand, the Generalitat de Catalunya (2014SGR-987), the Spanish Ministry of Economy and Competitiveness (CTQ2014-55174-P), and the Australian Research Council through a Future Fellowship. R.C.R thanks A*STAR Singapore for support. S.B. was supported by a Royal Golden Jubilee Ph.D. Scholarship (Grant PHD/106/2551) from the Thailand Research Fund. We acknowledge the computer support, technical expertise, and assistance provided by the Barcelona Supercomputing Center. Centro Nacional de Supercomputacion (BSC-CNS). Data collection was carried out at the National Synchrotron Radiation Research Center (NSRRC), a national user facility supported by the National Science Council of Taiwan, ROC. The Synchrotron Radiation Protein Crystallography Facility is supported by the National Research Program for Genomic Medicine.