4CD6

The structure of GH113 beta-mannanase AaManA from Alicyclobacillus acidocaldarius in complex with ManIFG

Summary for 4CD6

• Entry DOI: 10.2210/pdb4cd6/pdb
• Related: 4CD4 4CD5 4CD7 4CD8
• Descriptor: ENDO-BETA-1,4-MANNANASE, 5-HYDROXYMETHYL-3,4-DIHYDROXYPIPERIDINE, beta-D-mannopyranose, ... (4 entities in total)
• Functional Keywords: hydrolase, beta-mannosidase, mannosidase, glycoside hydrolase, gh26, gh113, cazy, enzyme-carbohydrate interaction, glycosidase inhibition, quantum mechanics, biocatalysis, conformation
• Biological source: ALICYCLOBACILLUS ACIDOCALDARIUS
• Total number of polymer chains: 1
• Total formula weight: 36670.29

Authors

Williams, R.J.,Iglesias-Fernandez, J.,Stepper, J.,Jackson, A.,Thompson, A.J.,Lowe, E.C.,White, J.M.,Gilbert, H.J.,Rovira, C.,Davies, G.J.,Williams, S.J. (deposition date: 2013-10-30, release date: 2014-04-02, Last modification date: 2023-12-20)

Primary citation

Williams, R.J.,Iglesias-Fernandez, J.,Stepper, J.,Jackson, A.,Thompson, A.J.,Lowe, E.C.,White, J.M.,Gilbert, H.J.,Rovira, C.,Davies, G.J.,Williams, S.J.
Combined Inhibitor Free-Energy Landscape and Structural Analysis Reports on the Mannosidase Conformational Coordinate.
Angew.Chem.Int.Ed.Engl., 53:1087-, 2014

PubMed Abstract: Mannosidases 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 β-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.

PubMed: 24339341
DOI: 10.1002/ANIE.201308334

Experimental method

X-RAY DIFFRACTION (1.64 Å)