2ze2

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 4: Line 4:
|PDB= 2ze2 |SIZE=350|CAPTION= <scene name='initialview01'>2ze2</scene>, resolution 2.90&Aring;
|PDB= 2ze2 |SIZE=350|CAPTION= <scene name='initialview01'>2ze2</scene>, resolution 2.90&Aring;
|SITE= <scene name='pdbsite=AC1:T27+Binding+Site+For+Residue+A+556'>AC1</scene>
|SITE= <scene name='pdbsite=AC1:T27+Binding+Site+For+Residue+A+556'>AC1</scene>
-
|LIGAND= <scene name='pdbligand=T27:'>T27</scene>
+
|LIGAND= <scene name='pdbligand=T27:4-{[4-({4-[(E)-2-CYANOETHENYL]-2,6-DIMETHYLPHENYL}AMINO)PYRIMIDIN-2-YL]AMINO}BENZONITRILE'>T27</scene>
|ACTIVITY=
|ACTIVITY=
|GENE= GAG-POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])
|GENE= GAG-POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])
 +
|DOMAIN=
 +
|RELATEDENTRY=[[2zd1|2ZD1]], [[3bgr|3BGR]], [[1s6q|1S6Q]], [[2ic3|2IC3]], [[1sv5|1SV5]]
 +
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ze2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ze2 OCA], [http://www.ebi.ac.uk/pdbsum/2ze2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ze2 RCSB]</span>
}}
}}
Line 27: Line 30:
[[Category: Jr., A D.Clark.]]
[[Category: Jr., A D.Clark.]]
[[Category: Shatkin, A J.]]
[[Category: Shatkin, A J.]]
-
[[Category: T27]]
 
[[Category: aid]]
[[Category: aid]]
[[Category: dapy]]
[[Category: dapy]]
Line 46: Line 48:
[[Category: transferase]]
[[Category: transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:53:55 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:20:37 2008''

Revision as of 02:20, 31 March 2008

Image:2ze2.jpg


PDB ID 2ze2

Drag the structure with the mouse to rotate
, resolution 2.90Å
Sites:
Ligands:
Gene: GAG-POL (Human immunodeficiency virus 1)
Related: 2ZD1, 3BGR, 1S6Q, 2IC3, 1SV5


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal structure of L100I/K103N mutant HIV-1 reverse transcriptase (RT) in complex with TMC278 (rilpivirine), a non-nucleoside RT inhibitor


Overview

TMC278 is a diarylpyrimidine (DAPY) nonnucleoside reverse transcriptase inhibitor (NNRTI) that is highly effective in treating wild-type and drug-resistant HIV-1 infections in clinical trials at relatively low doses ( approximately 25-75 mg/day). We have determined the structure of wild-type HIV-1 RT complexed with TMC278 at 1.8 A resolution, using an RT crystal form engineered by systematic RT mutagenesis. This high-resolution structure reveals that the cyanovinyl group of TMC278 is positioned in a hydrophobic tunnel connecting the NNRTI-binding pocket to the nucleic acid-binding cleft. The crystal structures of TMC278 in complexes with the double mutant K103N/Y181C (2.1 A) and L100I/K103N HIV-1 RTs (2.9 A) demonstrated that TMC278 adapts to bind mutant RTs. In the K103N/Y181C RT/TMC278 structure, loss of the aromatic ring interaction caused by the Y181C mutation is counterbalanced by interactions between the cyanovinyl group of TMC278 and the aromatic side chain of Y183, which is facilitated by an approximately 1.5 A shift of the conserved Y(183)MDD motif. In the L100I/K103N RT/TMC278 structure, the binding mode of TMC278 is significantly altered so that the drug conforms to changes in the binding pocket primarily caused by the L100I mutation. The flexible binding pocket acts as a molecular "shrink wrap" that makes a shape complementary to the optimized TMC278 in wild-type and drug-resistant forms of HIV-1 RT. The crystal structures provide a better understanding of how the flexibility of an inhibitor can compensate for drug-resistance mutations.

About this Structure

2ZE2 is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.

Reference

High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations., Das K, Bauman JD, Clark AD Jr, Frenkel YV, Lewi PJ, Shatkin AJ, Hughes SH, Arnold E, Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1466-71. Epub 2008 Jan 29. PMID:18230722

Page seeded by OCA on Mon Mar 31 05:20:37 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ze2"
Personal tools