2WW0

Structure of the Family GH92 Inverting Mannosidase BT3990 from Bacteroides thetaiotaomicron VPI-5482

Summary for 2WW0

• Entry DOI: 10.2210/pdb2ww0/pdb
• Related: 2WVX 2WVZ 2WW1 2WW3 2WX8
• Descriptor: PUTATIVE ALPHA-1,2-MANNOSIDASE, CALCIUM ION, 1S-8AB-OCTAHYDRO-INDOLIZIDINE-1A,2A,8B-TRIOL, ... (5 entities in total)
• Functional Keywords: hydrolase, gh92, bt3990, glycoside hydrolase family 92
• Biological source: BACTEROIDES THETAIOTAOMICRON
• Total number of polymer chains: 8
• Total formula weight: 688798.77

Authors

Suits, M.D.L.,Thompson, A.,Zhu, Y.,Gilbert, H.J.,Davies, G.J. (deposition date: 2009-10-21, release date: 2009-12-29, Last modification date: 2023-12-20)

Primary citation

Zhu, Y.,Suits, M.D.L.,Thompson, A.,Chavan, S.,Dinev, Z.,Dumon, C.,Smith, N.,Moremen, K.W.,Xiang, Y.,Siriwardena, A.,Williams, S.J.,Gilbert, H.J.,Davies, G.J.
Mechanistic Insights Into a Ca2+-Dependent Family of A-Mannosidases in a Human Gut Symbiont.
Nat.Chem.Biol., 6:125-, 2010

PubMed Abstract: Colonic bacteria, exemplified by Bacteroides thetaiotaomicron, play a key role in maintaining human health by harnessing large families of glycoside hydrolases (GHs) to exploit dietary polysaccharides and host glycans as nutrients. Such GH family expansion is exemplified by the 23 family GH92 glycosidases encoded by the B. thetaiotaomicron genome. Here we show that these are alpha-mannosidases that act via a single displacement mechanism to utilize host N-glycans. The three-dimensional structure of two GH92 mannosidases defines a family of two-domain proteins in which the catalytic center is located at the domain interface, providing acid (glutamate) and base (aspartate) assistance to hydrolysis in a Ca(2+)-dependent manner. The three-dimensional structures of the GH92s in complex with inhibitors provide insight into the specificity, mechanism and conformational itinerary of catalysis. Ca(2+) plays a key catalytic role in helping distort the mannoside away from its ground-state (4)C(1) chair conformation toward the transition state.

PubMed: 20081828
DOI: 10.1038/NCHEMBIO.278

Experimental method

X-RAY DIFFRACTION (2.8 Å)