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3upj
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=U03:4-HYDROXY-7-METHOXY-3-(1-PHENYL-PROPYL)-CHROMEN-2-ONE'>U03</scene> | |LIGAND= <scene name='pdbligand=U03:4-HYDROXY-7-METHOXY-3-(1-PHENYL-PROPYL)-CHROMEN-2-ONE'>U03</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3upj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upj OCA], [http://www.ebi.ac.uk/pdbsum/3upj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3upj RCSB]</span> | ||
}} | }} | ||
| Line 16: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 3UPJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ | + | 3UPJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_2 Human immunodeficiency virus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPJ 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://www.ncbi.nlm.nih.gov/pubmed/7658450 7658450] | 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 | + | [[Category: Human immunodeficiency virus 2]] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Janakiraman, M N.]] | [[Category: Janakiraman, M N.]] | ||
[[Category: Mulichak, A M.]] | [[Category: Mulichak, A M.]] | ||
[[Category: Watenpaugh, K D.]] | [[Category: Watenpaugh, K D.]] | ||
| - | [[Category: U03]] | ||
[[Category: hydrolase (acid protease)]] | [[Category: hydrolase (acid protease)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:36:30 2008'' |
Revision as of 02:36, 31 March 2008
| |||||||
| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | HIV-1 retropepsin, with EC number 3.4.23.16 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN IMMUNODEFICIENCY VIRUS TYPE 2 PROTEASE MUTANT WITH LYS 57 REPLACED BY LEU (K57L) COMPLEX WITH U096333 [4-HYDROXY-3-[1-(PHENYL)PROPYL]-7-METHOXYCOUMARIN]
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
3UPJ is a Single protein structure of sequence from Human immunodeficiency virus 2. 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 Mon Mar 31 05:36:30 2008
