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Structural snapshots for mechanism-based inactivation of a glycoside hydrolase by cyclopropyl carbasugars
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dc.contributor.author | Adamson, Christopher | |
dc.contributor.author | Pengelly, Robert J. | |
dc.contributor.author | Kazem Abadi, Saeideh Shamsi | |
dc.contributor.author | Chakladar, Saswati | |
dc.contributor.author | Draper, Jason | |
dc.contributor.author | Britton, Robert | |
dc.contributor.author | Gloster, Tracey M. | |
dc.contributor.author | Bennet, Andrew J. | |
dc.date.accessioned | 2016-11-04T09:30:13Z | |
dc.date.available | 2016-11-04T09:30:13Z | |
dc.date.issued | 2016-11-18 | |
dc.identifier | 247062907 | |
dc.identifier | 5582c897-abae-400f-bcaf-eb2f41cf1062 | |
dc.identifier | 84995802994 | |
dc.identifier | 000388258000012 | |
dc.identifier.citation | Adamson , C , Pengelly , R J , Kazem Abadi , S S , Chakladar , S , Draper , J , Britton , R , Gloster , T M & Bennet , A J 2016 , ' Structural snapshots for mechanism-based inactivation of a glycoside hydrolase by cyclopropyl carbasugars ' , Angewandte Chemie International Edition , vol. 55 , no. 48 , pp. 14978-14982 . https://doi.org/10.1002/anie.201607431 | en |
dc.identifier.issn | 1433-7851 | |
dc.identifier.uri | https://hdl.handle.net/10023/9763 | |
dc.description | This work was supported by an NSERC Discovery Grant (AJB: #121348-2012), a Wellcome Trust Career Development Fellowship (TMG: grant 095828), a Wellcome Trust Institutional Strategic Support award (TMG and RJP), a MSFHR Career Investigator Award (RB), a NSERC Discovery Grant (RB), and an NSERC PGSM Scholarship (CA). | en |
dc.description.abstract | 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 2H3 conformations. We also report the synthesis and reactivity of a fluorinated analogue and the structure of its covalently linked intermediate (flattened 2H3 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. | |
dc.format.extent | 2613993 | |
dc.language.iso | eng | |
dc.relation.ispartof | Angewandte Chemie International Edition | en |
dc.subject | Carbocycles | en |
dc.subject | Enzyme mechanisms | en |
dc.subject | Glycoside hydrolase | en |
dc.subject | Inhibitors | en |
dc.subject | X-ray crystallography | en |
dc.subject | QD Chemistry | en |
dc.subject | BDC | en |
dc.subject.lcc | QD | en |
dc.title | Structural snapshots for mechanism-based inactivation of a glycoside hydrolase by cyclopropyl carbasugars | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | 10.1002/anie.201607431 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 095828/Z/11/Z | en |
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