Distortion of mannoimidazole supports a: B 2,5 boat transition state for the family GH125 α-1,6-mannosidase from Clostridium perfringens

A Males; G Speciale; SJ Williams; GJ Davies

Journal article

Distortion of mannoimidazole supports a: B 2,5 boat transition state for the family GH125 α-1,6-mannosidase from Clostridium perfringens

A Males, G Speciale, SJ Williams, GJ Davies

Organic and Biomolecular Chemistry | ROYAL SOC CHEMISTRY | Published : 2019

DOI: 10.1039/c9ob01161g

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Abstract

Enzyme transition-state mimics can act as powerful inhibitors and allow structural studies that report on the conformation of the transition-state. Here, mannoimidazole, a mimic of the transition state of mannosidase catalyzed hydrolysis of mannosides, is shown to bind in a B2,5 conformation on the Clostridium perfringens GH125 α-1,6-mannosidase, providing additional evidence of a OS2-B2,5-1S5 conformational itinerary for enzymes of this family.

University of Melbourne Researchers

Spencer Williams Author

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Awarded by UK Research and Innovation

Funding Acknowledgements

This research was funded by Biotechnology and Biological Sciences Research Council (grant BB/M011151/1) for support AM. SJW is funded by the Australian Research Council (DP180101957, DP160100597). GJD is the Royal Society Ken Murray Research Professor. We thank Diamond Light Source for access to beamline I24 (proposal number mx-9948-71) that contributed to the results presented here and Johan Turkenburg and Sam Hart for coordinating data collection. PDB accession code: 6RQK. We would also like to thank Zach Armstrong for support with the IC<INF>50</INF> enzyme assay.