This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1bqn

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1bqn.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1bqn.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1bqn| PDB=1bqn | SCENE= }}
{{STRUCTURE_1bqn| PDB=1bqn | SCENE= }}
-
'''TYR 188 LEU HIV-1 RT/HBY 097'''
+
===TYR 188 LEU HIV-1 RT/HBY 097===
-
==Overview==
+
<!--
-
The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroqui noxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HBY 097 selects for unusual drug-resistance mutations in HIV-1 RT (e.g. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. We have determined the structure of HBY 097 complexed with wild-type HIV-1 RT at 3.1 A resolution. The HIV-1 RT/HBY 097 structure reveals an overall inhibitor geometry and binding mode differing significantly from RT/NNRTI structures reported earlier, in that HBY 097 does not adopt the usual butterfly-like shape. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution. HBY 097 binds to the mutant RT in a manner similar to that seen in the wild-type RT/HBY 097 complex, although there are some repositioning and conformational alterations of the inhibitor. Conformational changes of the structural elements forming the inhibitor-binding pocket, including the orientation of some side-chains, are observed. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant. The loss of binding energy may be partially offset by additional contacts resulting from conformational changes of the inhibitor and nearby amino acid residues. This would suggest that inhibitor flexibility can help to minimize drug resistance.
+
The line below this paragraph, {{ABSTRACT_PUBMED_9813120}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 9813120 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_9813120}}
==About this Structure==
==About this Structure==
Line 32: Line 36:
[[Category: Nucleotidyltransferase]]
[[Category: Nucleotidyltransferase]]
[[Category: Rna-directed dna polymerase]]
[[Category: Rna-directed dna polymerase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:50:29 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:32:44 2008''

Revision as of 16:32, 30 June 2008

Image:1bqn.png

Template:STRUCTURE 1bqn

TYR 188 LEU HIV-1 RT/HBY 097

Template:ABSTRACT PUBMED 9813120

About this Structure

1BQN is a Protein complex structure of sequences from Human immunodeficiency virus 1 and Human immunodeficiency virus type 1 (isolate 12). Full crystallographic information is available from OCA.

Reference

Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance., Hsiou Y, Das K, Ding J, Clark AD Jr, Kleim JP, Rosner M, Winkler I, Riess G, Hughes SH, Arnold E, J Mol Biol. 1998 Nov 27;284(2):313-23. PMID:9813120

Page seeded by OCA on Mon Jun 30 19:32:44 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bqn"
Personal tools