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2q54
From Proteopedia
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| - | [[Image:2q54.jpg|left|200px]] | + | [[Image:2q54.jpg|left|200px]] |
| - | + | ||
| - | '''Crystal structure of KB73 bound to HIV-1 protease''' | + | {{Structure |
| + | |PDB= 2q54 |SIZE=350|CAPTION= <scene name='initialview01'>2q54</scene>, resolution 1.85Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene> and <scene name='pdbligand=MU1:N~2~-ACETYL-N-[(1S,3S,4S)-4-({[(5S)-3-(3-ACETYLPHENYL)-2-OXO-1,3-OXAZOLIDIN-5-YL]CARBONYL}AMINO)-1-BENZYL-3-HYDROXY-5-PHENYLPENTYL]-L-VALINAMIDE'>MU1</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of KB73 bound to HIV-1 protease''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2Q54 is a [ | + | 2Q54 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q54 OCA]. |
==Reference== | ==Reference== | ||
| - | Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres., Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM, J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:[http:// | + | Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres., Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM, J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17696512 17696512] |
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 21: | Line 30: | ||
[[Category: hiv-1 protease]] | [[Category: hiv-1 protease]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | [[Category: protease | + | [[Category: protease inhibitor]] |
| - | ''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 18:21:51 2008'' |
Revision as of 16:21, 20 March 2008
| |||||||
| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | pol (Human immunodeficiency virus 1) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of KB73 bound to HIV-1 protease
Overview
A series of novel HIV-1 protease inhibitors based on two pseudosymmetric dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2' ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined. A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.
About this Structure
2Q54 is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres., Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM, J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. PMID:17696512
Page seeded by OCA on Thu Mar 20 18:21:51 2008
