4Q5M
D30N tethered HIV-1 protease dimer/saquinavir complex
Summary for 4Q5M
| Entry DOI | 10.2210/pdb4q5m/pdb |
| Related PRD ID | PRD_000454 |
| Descriptor | Protease, (2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide (3 entities in total) |
| Functional Keywords | hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human immunodeficiency virus type 1 (HIV-1) More |
| Cellular location | Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 |
| Total number of polymer chains | 1 |
| Total formula weight | 22571.63 |
| Authors | Prashar, V.,Bihani, S.C.,Ferrer, J.L.,Hosur, M.V. (deposition date: 2014-04-17, release date: 2015-04-08, Last modification date: 2023-11-08) |
| Primary citation | Prashar, V.,Bihani, S.C.,Ferrer, J.L.,Hosur, M.V. Structural Basis of Why Nelfinavir-Resistant D30N Mutant of HIV-1 Protease Remains Susceptible to Saquinavir. Chem.Biol.Drug Des., 86:302-308, 2015 Cited by PubMed Abstract: 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 Å 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. PubMed: 25487655DOI: 10.1111/cbdd.12494 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.795 Å) |
Structure validation
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