1dtt
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1dtt.gif|left|200px]] | + | [[Image:1dtt.gif|left|200px]] |
| - | + | ||
| - | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)''' | + | {{Structure |
| + | |PDB= 1dtt |SIZE=350|CAPTION= <scene name='initialview01'>1dtt</scene>, resolution 3.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=FTC:N-[[3-FLUORO-4-ETHOXY-PYRID-2-YL]ETHYL]-N'-[5-CHLORO-PYRIDYL]-THIOUREA'>FTC</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1DTT is a [ | + | 1DTT is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTT OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10681546 10681546] |
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| Line 26: | Line 35: | ||
[[Category: FTC]] | [[Category: FTC]] | ||
[[Category: drug design]] | [[Category: drug design]] | ||
| - | [[Category: hiv-1 reverse transcriptase | + | [[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 Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:44:11 2008'' |
Revision as of 08:44, 20 March 2008
| |||||||
| , resolution 3.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)
Overview
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 Structure
1DTT is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
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 Thu Mar 20 10:44:11 2008
