2O8M: Crystal Structure Of The S139a Mutant Of Hepatitis C Virus Ns3/4a Protease

Citation:
Abstract
The structures of both the native holo-HCV NS3/4A protease domain and the protease domain with a serine 139 to alanine (S139A) mutation were solved to high resolution. Subsequently, structures were determined for a series of ketoamide inhibitors in complex with the protease. The changes in the inhibitor potency were correlated with changes in the buried surface area upon binding the inhibitor to the active site. The largest contribution to the binding energy arises from the hydrophobic interactions of the P1 and P2 groups as they bind to the S1 and S2 pockets [the numbering of the subsites is as defined in Berger, A.; Schechter, I. Philos. Trans. R. Soc. London, Ser. B 1970, 257, 249-264]. This correlation of the changes in potency with increased buried surface area contributed directly to the design of a potent tripeptide inhibitor of the HCV NS3/4A protease that is currently in clinical trials.
PDB ID: 2O8MDownload
MMDB ID: 59175
PDB Deposition Date: 2006/12/12
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Hepacivirus C
Similar Structures:
Biological Unit for 2O8M: tetrameric; determined by author and by software (PISA)
Molecular Components in 2O8M
Label Count Molecule
Proteins (4 molecules)
2
Protease
Molecule annotation
2
Protease
Molecule annotation
Chemicals (4 molecules)
1
2
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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