5upj
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:5upj.gif|left|200px]] | [[Image:5upj.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_5upj", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_5upj| PDB=5upj | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''HIV-2 PROTEASE/U99283 COMPLEX''' | '''HIV-2 PROTEASE/U99283 COMPLEX''' | ||
| Line 29: | Line 26: | ||
[[Category: Mulichak, A M.]] | [[Category: Mulichak, A M.]] | ||
[[Category: Watenpaugh, K D.]] | [[Category: Watenpaugh, K D.]] | ||
| - | [[Category: | + | [[Category: Acid protease]] |
| - | [[Category: | + | [[Category: Aspartyl protease]] |
| - | [[Category: | + | [[Category: Hiv-2 protease/inhibitor complex]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Protein-substrate interaction]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:38:29 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:38, 4 May 2008
HIV-2 PROTEASE/U99283 COMPLEX
Overview
A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9), conformationally-flexible, alkyl rings, the enzyme inhibitory activity of the resulting compounds was dramatically improved, and inhibitors with more than 50-fold better binding (e.g., 5d, Ki = 0.015 microM) were obtained. X-ray crystal structures of these inhibitors complexed with HIV protease indicated the cycloalkyl rings were able to fold into the S1' pocket of the enzyme and fill it much more effectively than the rigid benzene ring of the 4-hydroxycoumarin compound. This work has resulted in the identification of a promising lead structure for the design of potent, deliverable HIV protease inhibitors. Compound 5d, a small (MW = 324), nonpeptidic structure, has already shown several advantages over peptidic inhibitors, including high oral bioavailability (91-99%), a relatively long half-life (4.9 h), and ease of synthesis (three steps).
About this Structure
5UPJ is a Single protein structure of sequence from Human immunodeficiency virus 2. Full crystallographic information is available from OCA.
Reference
Use of medium-sized cycloalkyl rings to enhance secondary binding: discovery of a new class of human immunodeficiency virus (HIV) protease inhibitors., Romines KR, Watenpaugh KD, Tomich PK, Howe WJ, Morris JK, Lovasz KD, Mulichak AM, Finzel BC, Lynn JC, Horng MM, et al., J Med Chem. 1995 May 26;38(11):1884-91. PMID:7783120 Page seeded by OCA on Sun May 4 22:38:29 2008
