1n5y: Difference between revisions

Revision as of 15:02, 21 February 2008

HIV-1 Reverse Transcriptase Crosslinked to Post-Translocation AZTMP-Terminated DNA (Complex P)

OverviewOverview

AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase. This reaction can occur when an AZTMP-terminated primer is bound at the nucleotide-binding site (pre-translocation complex N) but not at the 'priming' site (post-translocation complex P). We determined the crystal structures of N and P complexes at 3.0 and 3.1 A resolution. These structures provide insight into the structural basis of AZTMP excision and the mechanism of translocation. Docking of a dNTP in the P complex structure suggests steric crowding in forming a stable ternary complex that should increase the relative amount of the N complex, which is the substrate for excision. Structural differences between complexes N and P suggest that the conserved YMDD loop is involved in translocation, acting as a springboard that helps to propel the primer terminus from the N to the P site after dNMP incorporation.

About this StructureAbout this Structure

1N5Y is a Protein complex structure of sequences from Human immunodeficiency virus 1 and Mus musculus with as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.

ReferenceReference

Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA., Sarafianos SG, Clark AD Jr, Das K, Tuske S, Birktoft JJ, Ilankumaran P, Ramesha AR, Sayer JM, Jerina DM, Boyer PL, Hughes SH, Arnold E, EMBO J. 2002 Dec 2;21(23):6614-24. PMID:12456667

Page seeded by OCA on Thu Feb 21 14:02:38 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1n5y.gif|left|200px]]<br />
+[[Image:1n5y.gif|left|200px]]<br /><applet load="1n5y" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1n5y" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1n5y, resolution 3.10&Aring;" />
 '''HIV-1 Reverse Transcriptase Crosslinked to Post-Translocation AZTMP-Terminated DNA (Complex P)'''<br />
 ==Overview==
-AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision, of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase., This reaction can occur when an AZTMP-terminated primer is bound at the, nucleotide-binding site (pre-translocation complex N) but not at the, 'priming' site (post-translocation complex P). We determined the crystal, structures of N and P complexes at 3.0 and 3.1 A resolution. These, structures provide insight into the structural basis of AZTMP excision and, the mechanism of translocation. Docking of a dNTP in the P complex, structure suggests steric crowding in forming a stable ternary complex, that should increase the relative amount of the N complex, which is the, substrate for excision. Structural differences between complexes N and P, suggest that the conserved YMDD loop is involved in translocation, acting, as a springboard that helps to propel the primer terminus from the N to, the P site after dNMP incorporation.
+AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase. This reaction can occur when an AZTMP-terminated primer is bound at the nucleotide-binding site (pre-translocation complex N) but not at the 'priming' site (post-translocation complex P). We determined the crystal structures of N and P complexes at 3.0 and 3.1 A resolution. These structures provide insight into the structural basis of AZTMP excision and the mechanism of translocation. Docking of a dNTP in the P complex structure suggests steric crowding in forming a stable ternary complex that should increase the relative amount of the N complex, which is the substrate for excision. Structural differences between complexes N and P suggest that the conserved YMDD loop is involved in translocation, acting as a springboard that helps to propel the primer terminus from the N to the P site after dNMP incorporation.
 ==About this Structure==
-N5Y 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] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N5Y OCA].
+N5Y 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] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=1N5Y OCA].
 ==Reference==
@@ Line 17: / Line 16: @@
 [[Category: RNA-directed DNA polymerase]]
 [[Category: Arnold, E.]]
-[[Category: Birktoft, J.J.]]
+[[Category: Birktoft, J J.]]
-[[Category: Boyer, P.L.]]
+[[Category: Boyer, P L.]]
 [[Category: Das, K.]]
-[[Category: Hughes, S.H.]]
+[[Category: Hughes, S H.]]
 [[Category: Ilankumaran, P.]]
-[[Category: Jerina, D.M.]]
+[[Category: Jerina, D M.]]
-[[Category: Jr., A.D.Clark.]]
+[[Category: Jr., A D.Clark.]]
-[[Category: Ramesha, A.R.]]
+[[Category: Ramesha, A R.]]
-[[Category: Sarafianos, S.G.]]
+[[Category: Sarafianos, S G.]]
-[[Category: Sayer, J.M.]]
+[[Category: Sayer, J M.]]
 [[Category: Tuske, S.]]
 [[Category: MG]]
@@ Line 35: / Line 34: @@
 [[Category: translocation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov  8 14:21:22 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:38 2008''