1rt2
From Proteopedia
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| - | [[Image:1rt2.jpg|left|200px]] | + | [[Image:1rt2.jpg|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH TNK-651''' | + | {{Structure |
| + | |PDB= 1rt2 |SIZE=350|CAPTION= <scene name='initialview01'>1rt2</scene>, resolution 2.55Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=TNK:6-BENZYL-1-BENZYLOXYMETHYL-5-ISOPROPYL URACIL'>TNK</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= HIV-1 POL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 Human immunodeficiency virus 1]) | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH TNK-651''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RT2 is a [ | + | 1RT2 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=1RT2 OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/8648598 8648598] |
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: nucleotidyltransferase]] | [[Category: nucleotidyltransferase]] | ||
| - | ''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 13:55:47 2008'' |
Revision as of 11:55, 20 March 2008
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| , resolution 2.55Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | HIV-1 POL (Human immunodeficiency virus 1) | ||||||
| Activity: | RNA-directed DNA polymerase, with EC number 2.7.7.49 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH TNK-651
Overview
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 Structure
1RT2 is a Protein complex structure of sequences from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
Reference
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
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