4cd6
The structure of GH113 beta-mannanase AaManA from Alicyclobacillus acidocaldarius in complex with ManIFGThe structure of GH113 beta-mannanase AaManA from Alicyclobacillus acidocaldarius in complex with ManIFG
Structural highlights
FunctionPublication Abstract from PubMedMannosidases catalyze the hydrolysis of a diverse range of polysaccharides and glycoconjugates, and the various sequence-based mannosidase families have evolved ingenious strategies to overcome the stereoelectronic challenges of mannoside chemistry. Using a combination of computational chemistry, inhibitor design and synthesis, and X-ray crystallography of inhibitor/enzyme complexes, it is demonstrated that mannoimidazole-type inhibitors are energetically poised to report faithfully on mannosidase transition-state conformation, and provide direct evidence for the conformational itinerary used by diverse mannosidases, including beta-mannanases from families GH26 and GH113. Isofagomine-type inhibitors are poor mimics of transition-state conformation, owing to the high energy barriers that must be crossed to attain mechanistically relevant conformations, however, these sugar-shaped heterocycles allow the acquisition of ternary complexes that span the active site, thus providing valuable insight into active-site residues involved in substrate recognition. Combined inhibitor free-energy landscape and structural analysis reports on the mannosidase conformational coordinate.,Williams RJ, Iglesias-Fernandez J, Stepper J, Jackson A, Thompson AJ, Lowe EC, White JM, Gilbert HJ, Rovira C, Davies GJ, Williams SJ Angew Chem Int Ed Engl. 2014 Jan 20;53(4):1087-91. doi: 10.1002/anie.201308334., Epub 2013 Dec 11. PMID:24339341[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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