4yz5

Crystal Structure of Streptococcus pneumoniae NanC, in complex with 3-Sialyllactose

spinqualitylabelsall models 4yz5, resolution 2.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yz5 is a 2 chain structure with sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.27Å Ligands: DAN, GAL, GLC, PRD_900025, SIA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0H2UQE4_STRPN Publication Abstract from PubMed Streptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from alpha2-3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-beta-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind alpha2-3- and alpha2-6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold. Streptococcus pneumoniae NanC: STRUCTURAL INSIGHTS INTO THE SPECIFICITY AND MECHANISM OF A SIALIDASE THAT PRODUCES A SIALIDASE INHIBITOR.,Owen CD, Lukacik P, Potter JA, Sleator O, Taylor GL, Walsh MA J Biol Chem. 2015 Nov 13;290(46):27736-48. doi: 10.1074/jbc.M115.673632. Epub, 2015 Sep 14. PMID:26370075 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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