1hmv
From Proteopedia
(New page: 200px<br /> <applet load="1hmv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hmv, resolution 3.2Å" /> '''THE STRUCTURE OF UNL...) |
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caption="1hmv, resolution 3.2Å" /> | caption="1hmv, resolution 3.2Å" /> | ||
'''THE STRUCTURE OF UNLIGANDED REVERSE TRANSCRIPTASE FROM THE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1'''<br /> | '''THE STRUCTURE OF UNLIGANDED REVERSE TRANSCRIPTASE FROM THE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the reverse transcriptase (RT) from the type 1 | + | The crystal structure of the reverse transcriptase (RT) from the type 1 human immunodeficiency virus has been determined at 3.2-A resolution. Comparison with complexes between RT and the polymerase inhibitor Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci. USA 90, 6320-6324] reveals changes associated with ligand binding. The enzyme is a heterodimer (p66/p51), with domains labeled "fingers," "thumb," "palm," and "connection" in both subunits, and a ribonuclease H domain in the larger subunit only. The most striking difference between RT and both complex structures is the change in orientation of the p66 thumb (approximately 33 degrees rotation). Smaller shifts relative to the core of the molecule were also found in other domains, including the p66 fingers and palm, which contain the polymerase active site. Within the polymerase catalytic region itself, there are no rearrangements between RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66 palm near the polymerase active site, a region that is well-packed hydrophobic core in the unliganded enzyme. Room for the drug is provided by movement of a small beta-sheet within the palm domain of the Nevirapine complex. The rearrangement within the palm and thumb, as well as domain shifts relative to the enzyme core, may prevent correct placement of the oligonucleotide substrate when the drug is bound. |
==About this Structure== | ==About this Structure== | ||
| - | 1HMV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1HMV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HMV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: RNA-directed DNA polymerase]] | [[Category: RNA-directed DNA polymerase]] | ||
| - | [[Category: Culp, J | + | [[Category: Culp, J S.]] |
[[Category: Debouck, C.]] | [[Category: Debouck, C.]] | ||
| - | [[Category: Gamblin, S | + | [[Category: Gamblin, S J.]] |
| - | [[Category: Harris, B | + | [[Category: Harris, B A.]] |
| - | [[Category: Harrison, S | + | [[Category: Harrison, S C.]] |
[[Category: Hellmig, B.]] | [[Category: Hellmig, B.]] | ||
[[Category: Ray, S.]] | [[Category: Ray, S.]] | ||
| - | [[Category: Rodgers, D | + | [[Category: Rodgers, D W.]] |
| - | [[Category: Woolf, D | + | [[Category: Woolf, D J.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: nucleotidyltransferase]] | [[Category: nucleotidyltransferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:50 2008'' |
Revision as of 11:02, 21 February 2008
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THE STRUCTURE OF UNLIGANDED REVERSE TRANSCRIPTASE FROM THE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
Overview
The crystal structure of the reverse transcriptase (RT) from the type 1 human immunodeficiency virus has been determined at 3.2-A resolution. Comparison with complexes between RT and the polymerase inhibitor Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci. USA 90, 6320-6324] reveals changes associated with ligand binding. The enzyme is a heterodimer (p66/p51), with domains labeled "fingers," "thumb," "palm," and "connection" in both subunits, and a ribonuclease H domain in the larger subunit only. The most striking difference between RT and both complex structures is the change in orientation of the p66 thumb (approximately 33 degrees rotation). Smaller shifts relative to the core of the molecule were also found in other domains, including the p66 fingers and palm, which contain the polymerase active site. Within the polymerase catalytic region itself, there are no rearrangements between RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66 palm near the polymerase active site, a region that is well-packed hydrophobic core in the unliganded enzyme. Room for the drug is provided by movement of a small beta-sheet within the palm domain of the Nevirapine complex. The rearrangement within the palm and thumb, as well as domain shifts relative to the enzyme core, may prevent correct placement of the oligonucleotide substrate when the drug is bound.
About this Structure
1HMV is a Protein complex structure of sequences from Human immunodeficiency virus 1 with as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
Reference
The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1., Rodgers DW, Gamblin SJ, Harris BA, Ray S, Culp JS, Hellmig B, Woolf DJ, Debouck C, Harrison SC, Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6. PMID:7532306
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