1rt1: Difference between revisions

Revision as of 07:52, 3 May 2008

CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH MKC-442

OverviewOverview

Crystal structures of HIV-1 reverse transcriptase (RT) complexed with a range of chemically diverse non-nucleoside inhibitors (NNIs) have shown a single pocket in which the inhibitors bind and details of the inhibitor-protein interactions. To delineate the structural requirements for an effective inhibitor, we have determined the structures of three closely related NNIs which vary widely in their potencies. Crystal structures of HIV-1 RT complexed with two very potent inhibitors, MKC-442 and TNK-651, at 2.55 angstroms resolution complement our previous analysis of the complex with the less effective inhibitor, HEPT. These structures reveal conformational changes which correlate with changes in potency. We suggest that a major determinant of increased potency in the analogues of HEPT is an improved interaction between residue Tyr181 in the protein and the 6-benzyl ring of the inhibitors which stabilizes the structure of the complex. This arises through a conformational switching of the protein structure triggered by the steric bulk of the 5-substituent of the inhibitor pyrimidine ring.

About this StructureAbout this Structure

1RT1 is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.

ReferenceReference

Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors., Hopkins AL, Ren J, Esnouf RM, Willcox BE, Jones EY, Ross C, Miyasaka T, Walker RT, Tanaka H, Stammers DK, Stuart DI, J Med Chem. 1996 Apr 12;39(8):1589-600. PMID:8648598 Page seeded by OCA on Sat May 3 07:52:25 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1rt1.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1rt1 |SIZE=350|CAPTION= <scene name='initialview01'>1rt1</scene>, resolution 2.55&Aring;
+The line below this paragraph, containing "STRUCTURE_1rt1", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=MKC:6-BENZYL-1-ETHOXYMETHYL-5-ISOPROPYL+URACIL'>MKC</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= HIV-1 POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1])
+-->
-|DOMAIN=
+{{STRUCTURE_1rt1|  PDB=1rt1  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rt1 OCA], [http://www.ebi.ac.uk/pdbsum/1rt1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rt1 RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH MKC-442'''
@@ Line 34: / Line 31: @@
 [[Category: Stuart, D.]]
 [[Category: Willcox, B.]]
-[[Category: hiv-1 reverse transcriptase]]
+[[Category: Hiv-1 reverse transcriptase]]
-[[Category: nucleotidyltransferase]]
+[[Category: Nucleotidyltransferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 07:52:25 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:32:28 2008''