1har: Difference between revisions

Revision as of 13:59, 21 February 2008

2.2 ANGSTROMS RESOLUTION STRUCTURE OF THE AMINO-TERMINAL HALF OF HIV-1 REVERSE TRANSCRIPTASE (FINGERS AND PALM SUBDOMAINS)

OverviewOverview

BACKGROUND: HIV-1 reverse transcriptase (RT) catalyzes the transformation of single-stranded viral RNA into double-stranded DNA, which is integrated into host cell chromosomes. The molecule is a heterodimer of two subunits, p51 and p66. The amino acid sequence of p51 is identical to the sequence of the amino-terminal subdomains of p66. Earlier crystallographic studies indicate that the RT molecule is flexible, which may explain the difficulty in obtaining high-resolution data for the intact protein. We have therefore determined the structure of a fragment of RT (RT216), which contains only the amino-terminal half of the RT molecule ('finger' and 'palm' subdomains). RESULTS: The crystal structure of RT216 has been refined at 2.2 A resolution to a crystallographic R-value of 20.8%. The structure is very similar to that of the corresponding part of the p66 subunit in the p66/p51 heterodimer, although there is a small difference in the relative orientation of the two subdomains compared with the structure of an RT-DNA-antibody fragment complex. There are a large number of stabilizing contacts (mainly hydrogen bonds and hydrophobic interactions) between the subdomains. The locations of conserved amino acids and the position of some important drug-resistant mutations are described. CONCLUSIONS: The RT216 structure provides detailed three-dimensional information of one important part of HIV-1 RT (including the critical active site residues). We propose a model to explain the inhibitory effect of non-nucleoside inhibitors, which partially accounts for their effect in terms of conformational changes of active site residues.

About this StructureAbout this Structure

1HAR is a Single protein structure of sequence from Human immunodeficiency virus 1. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.

ReferenceReference

2.2 A resolution structure of the amino-terminal half of HIV-1 reverse transcriptase (fingers and palm subdomains)., Unge T, Knight S, Bhikhabhai R, Lovgren S, Dauter Z, Wilson K, Strandberg B, Structure. 1994 Oct 15;2(10):953-61. PMID:7532533

Page seeded by OCA on Thu Feb 21 12:59:15 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1har.gif|left|200px]]<br />
+[[Image:1har.gif|left|200px]]<br /><applet load="1har" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1har" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1har, resolution 2.2&Aring;" />
 '''2.2 ANGSTROMS RESOLUTION STRUCTURE OF THE AMINO-TERMINAL HALF OF HIV-1 REVERSE TRANSCRIPTASE (FINGERS AND PALM SUBDOMAINS)'''<br />
 ==Overview==
-BACKGROUND: HIV-1 reverse transcriptase (RT) catalyzes the transformation, of single-stranded viral RNA into double-stranded DNA, which is integrated, into host cell chromosomes. The molecule is a heterodimer of two subunits, p51 and p66. The amino acid sequence of p51 is identical to the sequence, of the amino-terminal subdomains of p66. Earlier crystallographic studies, indicate that the RT molecule is flexible, which may explain the, difficulty in obtaining high-resolution data for the intact protein. We, have therefore determined the structure of a fragment of RT (RT216), which, contains only the amino-terminal half of the RT molecule ('finger' and, 'palm' subdomains). RESULTS: The crystal structure of RT216 has been, refined at 2.2 A resolution to a crystallographic R-value of 20.8%. The, structure is very similar to that of the corresponding part of the p66, subunit in the p66/p51 heterodimer, although there is a small difference, in the relative orientation of the two subdomains compared with the, structure of an RT-DNA-antibody fragment complex. There are a large number, of stabilizing contacts (mainly hydrogen bonds and hydrophobic, interactions) between the subdomains. The locations of conserved amino, acids and the position of some important drug-resistant mutations are, described. CONCLUSIONS: The RT216 structure provides detailed, three-dimensional information of one important part of HIV-1 RT (including, the critical active site residues). We propose a model to explain the, inhibitory effect of non-nucleoside inhibitors, which partially accounts, for their effect in terms of conformational changes of active site, residues.
+BACKGROUND: HIV-1 reverse transcriptase (RT) catalyzes the transformation of single-stranded viral RNA into double-stranded DNA, which is integrated into host cell chromosomes. The molecule is a heterodimer of two subunits, p51 and p66. The amino acid sequence of p51 is identical to the sequence of the amino-terminal subdomains of p66. Earlier crystallographic studies indicate that the RT molecule is flexible, which may explain the difficulty in obtaining high-resolution data for the intact protein. We have therefore determined the structure of a fragment of RT (RT216), which contains only the amino-terminal half of the RT molecule ('finger' and 'palm' subdomains). RESULTS: The crystal structure of RT216 has been refined at 2.2 A resolution to a crystallographic R-value of 20.8%. The structure is very similar to that of the corresponding part of the p66 subunit in the p66/p51 heterodimer, although there is a small difference in the relative orientation of the two subdomains compared with the structure of an RT-DNA-antibody fragment complex. There are a large number of stabilizing contacts (mainly hydrogen bonds and hydrophobic interactions) between the subdomains. The locations of conserved amino acids and the position of some important drug-resistant mutations are described. CONCLUSIONS: The RT216 structure provides detailed three-dimensional information of one important part of HIV-1 RT (including the critical active site residues). We propose a model to explain the inhibitory effect of non-nucleoside inhibitors, which partially accounts for their effect in terms of conformational changes of active site residues.
 ==About this Structure==
-HAR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HAR OCA].
+HAR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. 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=1HAR OCA].
 ==Reference==
@@ Line 20: / Line 19: @@
 [[Category: reverse transcriptase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:05:01 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:59:15 2008''