2upj
From Proteopedia
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| - | [[Image:2upj.jpg|left|200px]] | + | [[Image:2upj.jpg|left|200px]] |
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| - | '''HIV-1 PROTEASE COMPLEX WITH U100313 ([3-[[3-[CYCLOPROPYL [4-HYDROXY-2OXO-6-[1-(PHENYLMETHYL)PROPYL]-2H-PYRAN-3-YL] METHYL]PHENYL]AMINO]-3-OXO-PROPYL]CARBAMIC ACID TERT-BUTYL ESTER)''' | + | {{Structure |
| + | |PDB= 2upj |SIZE=350|CAPTION= <scene name='initialview01'>2upj</scene>, resolution 3.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=U02:[2-(3-{[6-(1-BENZYL-PROPYL)-4-HYDROXY-2-OXO-2H-PYRAN-3-YL]-CYCLOPROPYL-METHYL}-PHENYLCARBAMOYL)-ETHYL]-CARBAMIC ACID TERT-BUTYL ESTER'>U02</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= | ||
| + | }} | ||
| + | |||
| + | '''HIV-1 PROTEASE COMPLEX WITH U100313 ([3-[[3-[CYCLOPROPYL [4-HYDROXY-2OXO-6-[1-(PHENYLMETHYL)PROPYL]-2H-PYRAN-3-YL] METHYL]PHENYL]AMINO]-3-OXO-PROPYL]CARBAMIC ACID TERT-BUTYL ESTER)''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2UPJ is a [ | + | 2UPJ 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=2UPJ OCA]. |
==Reference== | ==Reference== | ||
| - | Structure-based design of novel HIV protease inhibitors: carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors., Thaisrivongs S, Watenpaugh KD, Howe WJ, Tomich PK, Dolak LA, Chong KT, Tomich CC, Tomasselli AG, Turner SR, Strohbach JW, et al., J Med Chem. 1995 Sep 1;38(18):3624-37. PMID:[http:// | + | Structure-based design of novel HIV protease inhibitors: carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors., Thaisrivongs S, Watenpaugh KD, Howe WJ, Tomich PK, Dolak LA, Chong KT, Tomich CC, Tomasselli AG, Turner SR, Strohbach JW, et al., J Med Chem. 1995 Sep 1;38(18):3624-37. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7658450 7658450] |
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
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[[Category: hydrolase (acid protease)]] | [[Category: hydrolase (acid protease)]] | ||
| - | ''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 18:39:44 2008'' |
Revision as of 16:39, 20 March 2008
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| , resolution 3.0Å | |||||||
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| Ligands: | |||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HIV-1 PROTEASE COMPLEX WITH U100313 ([3-[[3-[CYCLOPROPYL [4-HYDROXY-2OXO-6-[1-(PHENYLMETHYL)PROPYL]-2H-PYRAN-3-YL] METHYL]PHENYL]AMINO]-3-OXO-PROPYL]CARBAMIC ACID TERT-BUTYL ESTER)
Overview
The low oral bioavailability and rapid biliary excretion of peptide-derived HIV protease inhibitors have limited their utility as potential therapeutic agents. Our broad screening program to discover nonpeptidic HIV protease inhibitors had previously identified compound II (phenprocoumon, K(i) = 1 muM) as a lead template. Crystal structures of HIV protease complexes containing the peptide-derived inhibitor I (1-(naphthoxyacetyl)-L-histidyl-5(S)-amino-6-cyclohexyl-3 (R),4(R)-dihydroxy-2(R)-isopropylhexanoyl-L-isoleucine N-(2-pyridylmethyl)amide) and nonpeptidic inhibitors, such as phenprocoumon (compound II), provided a rational basis for the structure-based design of more active analogues. This investigation reports on the important finding of a carboxamide functionally appropriately added to the 4-hydroxycoumarin and the 4-hydroxy-2-pyrone templates which resulted in a new promising series of nonpeptidic HIV protease inhibitors with improved enzyme-binding affinity. The most active diastereomer of the carboxamide-containing compound XXIV inhibited HIV-1 protease with a K(i) value of 0.0014 muM. This research provides a new design direction for the discovery of more potent HIV protease inhibitors as potential therapeutic agents for the treatment of HIV infection.
About this Structure
2UPJ 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 protease inhibitors: carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors., Thaisrivongs S, Watenpaugh KD, Howe WJ, Tomich PK, Dolak LA, Chong KT, Tomich CC, Tomasselli AG, Turner SR, Strohbach JW, et al., J Med Chem. 1995 Sep 1;38(18):3624-37. PMID:7658450
Page seeded by OCA on Thu Mar 20 18:39:44 2008
