2hb3
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2hb3.gif|left|200px]] | + | [[Image:2hb3.gif|left|200px]] |
| - | + | ||
| - | '''Wild-type HIV-1 Protease in complex with potent inhibitor GRL06579''' | + | {{Structure |
| + | |PDB= 2hb3 |SIZE=350|CAPTION= <scene name='initialview01'>2hb3</scene>, resolution 1.35Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=GRL:(3AS,5R,6AR)-HEXAHYDRO-2H-CYCLOPENTA[B]FURAN-5-YL+(2S,3S)-3-HYDROXY-4-(4-(HYDROXYMETHYL)-N-ISOBUTYLPHENYLSULFONAMIDO)-1-PHENYLBUTAN-2-YLCARBAMATE'>GRL</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Chymosin Chymosin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.4 3.4.23.4] | ||
| + | |GENE= GAG, POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | }} | ||
| + | |||
| + | '''Wild-type HIV-1 Protease in complex with potent inhibitor GRL06579''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2HB3 is a [ | + | 2HB3 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=2HB3 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance., Ghosh AK, Sridhar PR, Leshchenko S, Hussain AK, Li J, Kovalevsky AY, Walters DE, Wedekind JE, Grum-Tokars V, Das D, Koh Y, Maeda K, Gatanaga H, Weber IT, Mitsuya H, J Med Chem. 2006 Aug 24;49(17):5252-61. PMID:[http:// | + | Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance., Ghosh AK, Sridhar PR, Leshchenko S, Hussain AK, Li J, Kovalevsky AY, Walters DE, Wedekind JE, Grum-Tokars V, Das D, Koh Y, Maeda K, Gatanaga H, Weber IT, Mitsuya H, J Med Chem. 2006 Aug 24;49(17):5252-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16913714 16913714] |
[[Category: Chymosin]] | [[Category: Chymosin]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
| Line 22: | Line 31: | ||
[[Category: active-site cavity protease inhibitor catalytic aspartic acid]] | [[Category: active-site cavity protease inhibitor catalytic aspartic acid]] | ||
| - | ''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 17:15:00 2008'' |
Revision as of 15:15, 20 March 2008
| |||||||
| , resolution 1.35Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | GAG, POL (Human immunodeficiency virus 1) | ||||||
| Activity: | Chymosin, with EC number 3.4.23.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Wild-type HIV-1 Protease in complex with potent inhibitor GRL06579
Overview
Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.
About this Structure
2HB3 is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance., Ghosh AK, Sridhar PR, Leshchenko S, Hussain AK, Li J, Kovalevsky AY, Walters DE, Wedekind JE, Grum-Tokars V, Das D, Koh Y, Maeda K, Gatanaga H, Weber IT, Mitsuya H, J Med Chem. 2006 Aug 24;49(17):5252-61. PMID:16913714
Page seeded by OCA on Thu Mar 20 17:15:00 2008
