5upj

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:5upj.gif|left|200px]]
+
{{Seed}}
 +
[[Image:5upj.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_5upj| PDB=5upj | SCENE= }}
{{STRUCTURE_5upj| PDB=5upj | SCENE= }}
-
'''HIV-2 PROTEASE/U99283 COMPLEX'''
+
===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).
+
The line below this paragraph, {{ABSTRACT_PUBMED_7783120}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 7783120 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_7783120}}
==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Protein-substrate interaction]]
[[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 Thu Jul 3 14:12:59 2008''

Revision as of 11:12, 3 July 2008

Image:5upj.png

Template:STRUCTURE 5upj

HIV-2 PROTEASE/U99283 COMPLEX

Template:ABSTRACT PUBMED 7783120

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 Thu Jul 3 14:12:59 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5upj"
Personal tools