4Q5M: D30n Tethered Hiv-1 Protease Dimer/saquinavir Complex

Although anti-HIV-1 protease drugs nelfinavir (NFV) and saquinavir (SQV) share common functional groups, D30N is a major resistance mutation against NFV but remains susceptible to SQV. We have determined the crystal structure of D30N mutant-tethered HIV-1 protease in complex with SQV to 1.79 A resolution. Structural analysis showed that SQV forms two direct hydrogen bonds with the main chain atoms of the residues Asp29 and Asp30 that are not observed in the D30N-NFV complex. Apart from maintaining these two main chain hydrogen bonds, the P2-asparagine of SQV forms an additional hydrogen bond to the mutated side chain of the residue 30. These could be the reasons why D30N is not a drug resistance mutation against SQV. This structure supports the previous studies showing that the interactions between a potential inhibitor and backbone atoms of the enzyme are important to maintain potency against drug-resistant HIV-1 protease.
PDB ID: 4Q5MDownload
MMDB ID: 128383
PDB Deposition Date: 2014/4/17
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4Q5M: monomeric; determined by author and by software (PISA)
Molecular Components in 4Q5M
Label Count Molecule
Protein (1 molecule)
Protease(Gene symbol: gag-pol)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB