1dtt: Difference between revisions

Revision as of 14:16, 2 May 2008

CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)

OverviewOverview

Most non-nucleoside reverse transcriptase (RT) inhibitors are specific for HIV-1 RT and demonstrate minimal inhibition of HIV-2 RT. However, we report that members of the phenylethylthiazolylthiourea (PETT) series of non-nucleoside reverse transcriptase inhibitors showing high potency against HIV-1 RT have varying abilities to inhibit HIV-2 RT. Thus, PETT-1 inhibits HIV-1 RT with an IC(50) of 6 nM but shows only weak inhibition of HIV-2 RT, whereas PETT-2 retains similar potency against HIV-1 RT (IC(50) of 5 nM) and also inhibits HIV-2 RT (IC(50) of 2.2 microM). X-ray crystallographic structure determinations of PETT-1 and PETT-2 in complexes with HIV-1 RT reveal the compounds bind in an overall similar conformation albeit with some differences in their interactions with the protein. To investigate whether PETT-2 could be acting at a different site on HIV-2 RT (e.g. the dNTP or template primer binding site), we compared modes of inhibition for PETT-2 against HIV-1 and HIV-2 RT. PETT-2 was a noncompetitive inhibitor with respect to the dGTP substrate for both HIV-1 and HIV-2 RTs. PETT-2 was also a noncompetitive inhibitor with respect to a poly(rC).(dG) template primer for HIV-2 RT. These results are consistent with PETT-2 binding in corresponding pockets in both HIV-1 and HIV-2 RT with amino acid sequence differences in HIV-2 RT affecting the binding of PETT-2 compared with PETT-1.

About this StructureAbout this Structure

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

ReferenceReference

Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases. Structural and biochemical analyses., Ren J, Diprose J, Warren J, Esnouf RM, Bird LE, Ikemizu S, Slater M, Milton J, Balzarini J, Stuart DI, Stammers DK, J Biol Chem. 2000 Feb 25;275(8):5633-9. PMID:10681546 Page seeded by OCA on Fri May 2 14:16:00 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:1dtt.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1dtt |SIZE=350|CAPTION= <scene name='initialview01'>1dtt</scene>, resolution 3.0&Aring;
+The line below this paragraph, containing "STRUCTURE_1dtt", 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=CSW:CYSTEINE-S-DIOXIDE'>CSW</scene>, <scene name='pdbligand=FTC:N-[[3-FLUORO-4-ETHOXY-PYRID-2-YL]ETHYL]-N&#39;-[5-CHLORO-PYRIDYL]-THIOUREA'>FTC</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1dtt|  PDB=1dtt  |  SCENE=  }}
-|RELATEDENTRY=[[1rtv|1rtv]], [[1rth|1rth]], [[1vru|1vru]], [[1rti|1rti]], [[1rtj|1rtj]], [[1rev|1rev]], [[1rt1|1rt1]], [[1rt2|1rt2]], [[1klm|1klm]], [[1rt3|1rt3]], [[1rt4|1rt4]], [[1rt5|1rt5]], [[1rt6|1rt6]], [[1rt7|1rt7]], [[1c0t|1c0t]], [[1c0u|1c0u]], [[1c1b|1c1b]], [[1c1c|1c1c]], [[1dtq|1dtq]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtt OCA], [http://www.ebi.ac.uk/pdbsum/1dtt PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dtt RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)'''
@@ Line 36: / Line 33: @@
 [[Category: Stuart, D I.]]
 [[Category: Warren, J.]]
-[[Category: drug design]]
+[[Category: Drug design]]
-[[Category: hiv-1 reverse transcriptase aid]]
+[[Category: Hiv-1 reverse transcriptase aid]]
-[[Category: non-nucleoside inhibitor]]
+[[Category: Non-nucleoside inhibitor]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:16:00 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:48:29 2008''