2idw
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2idw.gif|left|200px]] | + | [[Image:2idw.gif|left|200px]] |
| - | + | ||
| - | '''Crystal structure analysis of HIV-1 protease mutant V82A with a potent non-peptide inhibitor (UIC-94017)''' | + | {{Structure |
| + | |PDB= 2idw |SIZE=350|CAPTION= <scene name='initialview01'>2idw</scene>, resolution 1.10Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=017:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL(1S,2R)-3-[[(4-AMINOPHENYL)SULFONYL](ISOBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE'>017</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= gag, pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure analysis of HIV-1 protease mutant V82A with a potent non-peptide inhibitor (UIC-94017)''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2IDW is a [ | + | 2IDW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. This structure supersedes the now removed PDB entry 1S65. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IDW OCA]. |
==Reference== | ==Reference== | ||
| - | High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains., Tie Y, Boross PI, Wang YF, Gaddis L, Hussain AK, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT, J Mol Biol. 2004 Apr 23;338(2):341-52. PMID:[http:// | + | High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains., Tie Y, Boross PI, Wang YF, Gaddis L, Hussain AK, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT, J Mol Biol. 2004 Apr 23;338(2):341-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15066436 15066436] |
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
| Line 37: | Line 46: | ||
[[Category: uic-94017]] | [[Category: uic-94017]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:28:20 2008'' |
Revision as of 15:28, 20 March 2008
| |||||||
| , resolution 1.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , and | ||||||
| Gene: | gag, pol (Human immunodeficiency virus 1) | ||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure analysis of HIV-1 protease mutant V82A with a potent non-peptide inhibitor (UIC-94017)
Overview
The compound UIC-94017 (TMC-114) is a second-generation HIV protease inhibitor with improved pharmacokinetics that is chemically related to the clinical inhibitor amprenavir. UIC-94017 is a broad-spectrum potent inhibitor active against HIV-1 clinical isolates with minimal cytotoxicity. We have determined the high-resolution crystal structures of UIC-94017 in complexes with wild-type HIV-1 protease (PR) and mutant proteases PR(V82A) and PR(I84V) that are common in drug-resistant HIV. The structures were refined at resolutions of 1.10-1.53A. The crystal structures of PR and PR(I84V) with UIC-94017 ternary complexes show that the inhibitor binds to the protease in two overlapping positions, while the PR(V82A) complex had one ordered inhibitor. In all three structures, UIC-94017 forms hydrogen bonds with the conserved main-chain atoms of Asp29 and Asp30 of the protease. These interactions are proposed to be critical for the potency of this compound against HIV isolates that are resistant to multiple protease inhibitors. Other small differences were observed in the interactions of the mutants with UIC-94017 as compared to PR. PR(V82A) showed differences in the position of the main-chain atoms of residue 82 compared to PR structure that better accommodated the inhibitor. Finally, the 1.10A resolution structure of PR(V82A) with UIC-94017 showed an unusual distribution of electron density for the catalytic aspartate residues, which is discussed in relation to the reaction mechanism.
About this Structure
2IDW is a Single protein structure of sequence from Human immunodeficiency virus 1. This structure supersedes the now removed PDB entry 1S65. Full crystallographic information is available from OCA.
Reference
High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains., Tie Y, Boross PI, Wang YF, Gaddis L, Hussain AK, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT, J Mol Biol. 2004 Apr 23;338(2):341-52. PMID:15066436
Page seeded by OCA on Thu Mar 20 17:28:20 2008
Categories: HIV-1 retropepsin | Human immunodeficiency virus 1 | Single protein | Boross, P I. | Gaddis, L. | Ghosh, A K. | Harrison, R W. | Hussain, A K. | Leshchenko, S. | Louis, J M. | Manna, D. | Tie, Y. | Wang, Y F. | Weber, I T. | 017 | ACY | CL | DMS | GOL | PO4 | Dimer | Hiv-1 protease | Inhibitor | Mutant | Uic-94017
