2nnk
From Proteopedia
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|PDB= 2nnk |SIZE=350|CAPTION= <scene name='initialview01'>2nnk</scene>, resolution 1.25Å | |PDB= 2nnk |SIZE=350|CAPTION= <scene name='initialview01'>2nnk</scene>, resolution 1.25Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ROC:CIS-N-TERT-BUTYL-DECAHYDRO-2-[2(R)-HYDROXY-4-PHENYL-3(S)-[[N-2-QUINOLYLCARBONYL-L-ASPARAGINYL]AMINO]BUTYL]-(4AS)-ISOQUINOLINE-3(S)-CARBOXAMIDE'>ROC</scene> |
| - | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span> | |
|GENE= gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | |GENE= gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2nmw|2NMW]], [[2nmy|2NMY]], [[2nmz|2NMZ]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nnk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nnk OCA], [http://www.ebi.ac.uk/pdbsum/2nnk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nnk RCSB]</span> | ||
}} | }} | ||
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[[Category: Wang, Y F.]] | [[Category: Wang, Y F.]] | ||
[[Category: Weber, I T.]] | [[Category: Weber, I T.]] | ||
| - | [[Category: ACY]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: NA]] | ||
| - | [[Category: ROC]] | ||
[[Category: dimer]] | [[Category: dimer]] | ||
[[Category: hiv-1 protease]] | [[Category: hiv-1 protease]] | ||
| Line 43: | Line 41: | ||
[[Category: saquinavir]] | [[Category: saquinavir]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:05:35 2008'' |
Revision as of 01:05, 31 March 2008
| |||||||
| , resolution 1.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | gag (Human immunodeficiency virus 1) | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Related: | 2NMW, 2NMY, 2NMZ
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure analysis of HIV-1 protease mutant I84V with a inhibitor saquinavir
Overview
Saquinavir (SQV), the first antiviral HIV-1 protease (PR) inhibitor approved for AIDS therapy, has been studied in complexes with PR and the variants PR(I) (84V) and PR(V) (82A) containing the single mutations I84V and V82A that provide resistance to all the clinical inhibitors. Atomic resolution crystal structures (0.97-1.25 A) of the SQV complexes were analyzed in comparison to the protease complexes with darunavir, a new drug that targets resistant HIV, in order to understand the molecular basis of drug resistance. PR(I) (84V) and PR(V) (82A) complexes were obtained in both the space groups P2(1)2(1)2 and P2(1)2(1)2(1), which provided experimental limits for the conformational flexibility. The SQV interactions with PR were very similar in the mutant complexes, consistent with the similar inhibition constants. The mutation from bigger to smaller amino acids allows more space to accommodate the large group at P1' of SQV, unlike the reduced interactions observed in darunavir complexes. The residues 79-82 have adjusted to accommodate the large hydrophobic groups of SQV, suggesting that these residues are intrinsically flexible and their conformation depends more on the nature of the inhibitor than on the mutations in this region. This analysis will assist with development of more effective antiviral inhibitors.
About this Structure
2NNK is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir., Tie Y, Kovalevsky AY, Boross P, Wang YF, Ghosh AK, Tozser J, Harrison RW, Weber IT, Proteins. 2007 Apr 1;67(1):232-42. PMID:17243183
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