4YW5: Crystal Structure Of Streptococcus Pneumoniae Nanc, Complex With Oseltamivir Carboxylate

Citation:
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 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.
PDB ID: 4YW5Download
MMDB ID: 132845
PDB Deposition Date: 2015/3/20
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
Similar Structures:
Biological Unit for 4YW5: monomeric; determined by author
Molecular Components in 4YW5
Label Count Molecule
Protein (1 molecule)
1
Neuraminidase C
Molecule annotation
Chemicals (7 molecules)
1
1
2
5
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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