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| [[Image:2vmf.jpg|left|200px]] | | {{Seed}} |
| | [[Image:2vmf.png|left|200px]] |
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| {{STRUCTURE_2vmf| PDB=2vmf | SCENE= }} | | {{STRUCTURE_2vmf| PDB=2vmf | SCENE= }} |
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| '''STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES'''
| | ===STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES=== |
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| ==Overview==
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| Enzyme inhibition through mimicry of the transition state is a major area for the design of new therapeutic agents. Emerging evidence suggests that many retaining glycosidases that are active on alpha- or beta-mannosides harness unusual B2,5 (boat) transition states. Here we present the analysis of 25 putative beta-mannosidase inhibitors, whose Ki values range from nanomolar to millimolar, on the Bacteroides thetaiotaomicron beta-mannosidase BtMan2A. B2,5 or closely related conformations were observed for all tightly binding compounds. Subsequent linear free energy relationships that correlate log Ki with log Km/kcat for a series of active center variants highlight aryl-substituted mannoimidazoles as powerful transition state mimics in which the binding energy of the aryl group enhances both binding and the degree of transition state mimicry. Support for a B2,5 transition state during enzymatic beta-mannosidase hydrolysis should also facilitate the design and exploitation of transition state mimics for the inhibition of retaining alpha-mannosidases--an area that is emerging for anticancer therapeutics.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18408714}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18408714 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18408714}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Mannosidase]] | | [[Category: Mannosidase]] |
| [[Category: Transition state mimic]] | | [[Category: Transition state mimic]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:30:49 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:16:43 2008'' |