4YZ2
Crystal Structure of Streptococcus pneumoniae NanC, in complex with 2-deoxy-2,3-didehydro-N-acetylneuraminic acid.
Summary for 4YZ2
| Entry DOI | 10.2210/pdb4yz2/pdb |
| Descriptor | Sialidase NanC, 2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | sialidase, neuraminidase, beta-propeller, cbm40, hydrolase |
| Biological source | Streptococcus pneumoniae |
| Total number of polymer chains | 2 |
| Total formula weight | 153536.83 |
| Authors | Lukacik, P.,Owen, C.D.,Potter, J.A.,Taylor, G.L.,Walsh, M.A. (deposition date: 2015-03-24, release date: 2015-09-23, Last modification date: 2024-05-08) |
| Primary citation | Owen, C.D.,Lukacik, P.,Potter, J.A.,Sleator, O.,Taylor, G.L.,Walsh, M.A. Streptococcus pneumoniae NanC: STRUCTURAL INSIGHTS INTO THE SPECIFICITY AND MECHANISM OF A SIALIDASE THAT PRODUCES A SIALIDASE INHIBITOR. J.Biol.Chem., 290:27736-27748, 2015 Cited by PubMed Abstract: 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 α2-3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-β-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 α2-3- and α2-6-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. PubMed: 26370075DOI: 10.1074/jbc.M115.673632 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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