2VK6: The Structure of Clostridium Perfringens Nani Sialidase and ITS Catalytic Intermediates

Citation:
Abstract
Clostridium perfringens is a Gram-positive bacterium responsible for bacteremia, gas gangrene, and occasionally food poisoning. Its genome encodes three sialidases, nanH, nanI, and nanJ, that are involved in the removal of sialic acids from a variety of glycoconjugates and that play a role in bacterial nutrition and pathogenesis. Recent studies on trypanosomal (trans-) sialidases have suggested that catalysis in all sialidases may proceed via a covalent intermediate similar to that of other retaining glycosidases. Here we provide further evidence to support this suggestion by reporting the 0.97A resolution atomic structure of the catalytic domain of the C. perfringens NanI sialidase, and complexes with its substrate sialic acid (N-acetylneuramic acid) also to 0.97A resolution, with a transition-state analogue (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) to 1.5A resolution, and with a covalent intermediate formed using a fluorinated sialic acid analogue to 1.2A resolution. Together, these structures provide high resolution snapshots along the catalytic pathway. The crystal structures suggested that NanI is able to hydrate 2-deoxy-2,3-dehydro-N-acetylneuraminic acid to N-acetylneuramic acid. This was confirmed by NMR, and a mechanism for this activity is suggested.
PDB ID: 2VK6Download
MMDB ID: 62025
PDB Deposition Date: 2007/12/17
Updated in MMDB: 2012/09 
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit: monomeric; determined by author, and by software (PQS)
Molecular Components
Label Count Molecule
Protein (1 molecule)
1
Exo-alpha-sialidase
Molecule annotation
Chemicals (7 molecules)
1
1
2
1
3
4
4
1
* Click molecule labels to explore molecular sequence information.

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