2upj
From Proteopedia
(New page: 200px<br /> <applet load="2upj" size="450" color="white" frame="true" align="right" spinBox="true" caption="2upj, resolution 3.0Å" /> '''HIV-1 PROTEASE COMPL...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2upj. | + | [[Image:2upj.jpg|left|200px]]<br /><applet load="2upj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2upj" size=" | + | |
caption="2upj, resolution 3.0Å" /> | caption="2upj, resolution 3.0Å" /> | ||
'''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)'''<br /> | '''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)'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2UPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with U02 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2UPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=U02:'>U02</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UPJ OCA]. |
==Reference== | ==Reference== | ||
| Line 21: | Line 20: | ||
[[Category: hydrolase (acid protease)]] | [[Category: hydrolase (acid protease)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:42:38 2008'' |
Revision as of 15:42, 15 February 2008
|
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 with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 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 Fri Feb 15 17:42:38 2008
