4KB9: Crystal Structure Of Wild-type Hiv-1 Protease With Novel Tricyclic P2- Ligands Grl-0739a

Citation:
Abstract
The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2 ligands are described. Various substituent effects were investigated to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity, although the incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions, which may account for the inhibitor's potent antiviral activity and excellent resistance profiles.
PDB ID: 4KB9Download
MMDB ID: 113230
PDB Deposition Date: 2013/4/23
Updated in MMDB: 2013/09
Experimental Method:
x-ray diffraction
Resolution: 1.29  Å
Source Organism:
Similar Structures:
Biological Unit for 4KB9: dimeric; determined by author and by software (PISA)
Molecular Components in 4KB9
Label Count Molecule
Proteins (2 molecules)
2
Protease
Molecule annotation
Chemicals (9 molecules)
1
1
2
2
3
3
4
1
5
2
* Click molecule labels to explore molecular sequence information.

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