4BBW

The crystal structure of Sialidase VPI 5482 (BTSA) from Bacteroides thetaiotaomicron

Summary for 4BBW

• Entry DOI: 10.2210/pdb4bbw/pdb
• Descriptor: SIALIDASE (NEURAMINIDASE) (2 entities in total)
• Functional Keywords: hydrolase, neuramidase
• Biological source: BACTEROIDES THETAIOTAOMICRON
• Total number of polymer chains: 1
• Total formula weight: 61763.33

Authors

Park, K.-H.,Song, H.-N.,Jung, T.-Y.,Lee, M.-H.,Woo, E.-J. (deposition date: 2012-09-28, release date: 2013-08-14, Last modification date: 2024-10-16)

Primary citation

Park, K.,Kim, M.,Ahn, H.,Lee, D.,Kim, J.,Kim, Y.,Woo, E.
Structural and Biochemical Characterization of the Broad Substrate Specificity of Bacteroides Thetaiotaomicron Commensal Sialidase.
Biochim.Biophys.Acta, 1834:1510-, 2013

PubMed Abstract: Sialidases release the terminal sialic acid residue from a wide range of sialic acid-containing polysaccharides. Bacteroides thetaiotaomicron, a symbiotic commensal microbe, resides in and dominates the human intestinal tract. We characterized the recombinant sialidase from B. thetaiotaomicron (BTSA) and demonstrated that it has broad substrate specificity with a relative activity of 97, 100 and 64 for 2,3-, 2,6- and 2,8-linked sialic substrates, respectively. The hydrolysis activity of BTSA was inhibited by a transition state analogue, 2-deoxy-2,3-dehydro-N-acetyl neuraminic acid, by competitive inhibition with a Ki value of 35μM. The structure of BSTA was determined at a resolution of 2.3Å. This structure exhibited a unique carbohydrate-binding domain (CBM) at its N-terminus (a.a. 23-190) that is adjacent to the catalytic domain (a.a. 191-535). The catalytic domain has a conserved arginine triad with a wide-open entrance for the substrate that exposes the catalytic residue to the surface. Unlike other pathogenic sialidases, the polysaccharide-binding site in the CBM is near the active site and possibly holds and positions the polysaccharide substrate directly at the active site. The structural feature of a wide substrate-binding groove and closer proximity of the polysaccharide-binding site to the active site could be a unique signature of the commensal sialidase BTSA and provide a molecular basis for its pharmaceutical application.

PubMed: 23665536
DOI: 10.1016/J.BBAPAP.2013.04.028

Experimental method

X-RAY DIFFRACTION (2.3 Å)