Structural highlights
Publication Abstract from PubMed
Glycoside hydrolases (GHs) have attracted considerable attention as targets for therapeutic agents, and thus mechanism-based inhibitors are of great interest. We report the first structural analysis of a carbocyclic mechanism-based GH inactivator, the results of which show that the two Michaelis complexes are in 2 H3 conformations. We also report the synthesis and reactivity of a fluorinated analogue and the structure of its covalently linked intermediate (flattened 2 H3 half-chair). We conclude that these inactivator reactions mainly involve motion of the pseudo-anomeric carbon atom, knowledge that should stimulate the design of new transition-state analogues for use as chemical biology tools.
Structural Snapshots for Mechanism-Based Inactivation of a Glycoside Hydrolase by Cyclopropyl Carbasugars.,Adamson C, Pengelly RJ, Shamsi Kazem Abadi S, Chakladar S, Draper J, Britton R, Gloster TM, Bennet AJ Angew Chem Int Ed Engl. 2016 Nov 21;55(48):14978-14982. doi:, 10.1002/anie.201607431. Epub 2016 Oct 26. PMID:27783466[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Adamson C, Pengelly RJ, Shamsi Kazem Abadi S, Chakladar S, Draper J, Britton R, Gloster TM, Bennet AJ. Structural Snapshots for Mechanism-Based Inactivation of a Glycoside Hydrolase by Cyclopropyl Carbasugars. Angew Chem Int Ed Engl. 2016 Nov 21;55(48):14978-14982. doi:, 10.1002/anie.201607431. Epub 2016 Oct 26. PMID:27783466 doi:http://dx.doi.org/10.1002/anie.201607431
