From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1dtt.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1dtt.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1dtt| PDB=1dtt | SCENE= }} | | {{STRUCTURE_1dtt| PDB=1dtt | SCENE= }} |
| | | | |
| - | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)'''
| + | ===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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10681546}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10681546 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_10681546}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 36: |
Line 40: |
| | [[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 Mon Jun 30 23:36:16 2008'' |
Revision as of 20:36, 30 June 2008
Template:STRUCTURE 1dtt
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH PETT-2 (PETT130A94)
Template:ABSTRACT PUBMED 10681546
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 Mon Jun 30 23:36:16 2008
Categories: Human immunodeficiency virus 1 | Protein complex | Balzarini, J. | Bird, L E. | Diprose, J. | Esnouf, R M. | Ikemizu, S. | Milton, J. | Ren, J. | Slater, M. | Stammers, D K. | Stuart, D I. | Warren, J. | Drug design | Hiv-1 reverse transcriptase aid | Non-nucleoside inhibitor
