3A2O: Crystal Structure of HIV-1 Protease Complexed with KNI-1689

Citation:
Abstract
A series of HIV protease inhibitor based on the allophenylnorstatine structure with various P(2)' moieties were synthesized. Among these analogues, we discovered that a small allyl group would maintain potent enzyme inhibitory activity compared to the o-methylbenzyl moiety in clinical candidate 1 (KNI-764, also known as JE-2147, AG-1776, or SM-319777). Introduction of an anilinic amino group to 2 (KNI-727) improved water-solubility and anti-HIV-1 activity. X-ray crystallographic analysis of 13k (KNI-1689) with a beta-methallyl group at P(2)' position revealed hydrophobic interactions with Ala28, Ile84, and Ile50' similar to that of 1. The presence of an additional methyl group on the allyl group in compound 13k significantly increased anti-HIV activity over 1 while providing a rational drug design for structural minimization and improving membrane permeability.
PDB ID: 3A2ODownload
MMDB ID: 80389
PDB Deposition Date: 2009/5/26
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 0.88  Å
Source Organism:
Similar Structures:
Biological Unit for 3A2O: dimeric; determined by author and by software (PISA)
Molecular Components in 3A2O
Label Count Molecule
Proteins (2 molecules)
2
Protease
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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