4I31: Crystal Structure Of Hcv Ns3/ns4a Protease Complexed With Compound 4

Citation:
Abstract
Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms.
PDB ID: 4I31Download
MMDB ID: 106330
PDB Deposition Date: 2012/11/23
Updated in MMDB: 2013/03
Experimental Method:
x-ray diffraction
Resolution: 1.93  Å
Source Organism:
Similar Structures:
Biological Unit for 4I31: dimeric; determined by author and by software (PISA)
Molecular Components in 4I31
Label Count Molecule
Proteins (2 molecules)
1
Genome Polyprotein
Molecule annotation
1
HCV Non-structural Protein 4A
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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