1gx6: Difference between revisions

Revision as of 18:07, 2 May 2008

HEPATITIS C VIRUS RNA POLYMERASE IN COMPLEX WITH UTP AND MANGANESE

OverviewOverview

We report here the results of a systematic high-resolution X-ray crystallographic analysis of complexes of the hepatitis C virus (HCV) RNA polymerase with ribonucleoside triphosphates (rNTPs) and divalent metal ions. An unexpected observation revealed by this study is the existence of a specific rGTP binding site in a shallow pocket at the molecular surface of the enzyme, 30 A away from the catalytic site. This previously unidentified rGTP pocket, which lies at the interface between fingers and thumb, may be an allosteric regulatory site and could play a role in allowing alternative interactions between the two domains during a possible conformational change of the enzyme required for efficient initiation. The electron density map at 1.7-A resolution clearly shows the mode of binding of the guanosine moiety to the enzyme. In the catalytic site, density corresponding to the triphosphates of nucleotides bound to the catalytic metals was apparent in each complex with nucleotides. Moreover, a network of triphosphate densities was detected; these densities superpose to the corresponding moieties of the nucleotides observed in the initiation complex reported for the polymerase of bacteriophage phi6, strengthening the proposal that the two enzymes initiate replication de novo by similar mechanisms. No equivalent of the protein stacking platform observed for the priming nucleotide in the phi6 enzyme is present in HCV polymerase, however, again suggesting that a change in conformation of the thumb domain takes place upon template binding to allow for efficient de novo initiation of RNA synthesis.

About this StructureAbout this Structure

1GX6 is a Single protein structure of sequence from Hepatitis c virus genotype 1b (isolate bk). Full crystallographic information is available from OCA.

ReferenceReference

Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides., Bressanelli S, Tomei L, Rey FA, De Francesco R, J Virol. 2002 Apr;76(7):3482-92. PMID:11884572 Page seeded by OCA on Fri May 2 18:07:45 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:1gx6.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1gx6 |SIZE=350|CAPTION= <scene name='initialview01'>1gx6</scene>, resolution 1.85&Aring;
+The line below this paragraph, containing "STRUCTURE_1gx6", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=UT1:Mn+Binding+Site+For+Chain+A'>UT1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=UTP:URIDINE+5&#39;-TRIPHOSPHATE'>UTP</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1gx6|  PDB=1gx6  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gx6 OCA], [http://www.ebi.ac.uk/pdbsum/1gx6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gx6 RCSB]</span>
-}}
 '''HEPATITIS C VIRUS RNA POLYMERASE IN COMPLEX WITH UTP AND MANGANESE'''
@@ Line 23: / Line 20: @@
 ==Reference==
 Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides., Bressanelli S, Tomei L, Rey FA, De Francesco R, J Virol. 2002 Apr;76(7):3482-92. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11884572 11884572]
-[[Category: Hepatitis c virus genotype 1b (isolate bk)]]
 [[Category: RNA-directed RNA polymerase]]
 [[Category: Single protein]]
@@ Line 29: / Line 25: @@
 [[Category: Rey, F A.]]
 [[Category: 3d-structure.]]
-[[Category: atp-binding]]
+[[Category: Atp-binding]]
-[[Category: coat protein]]
+[[Category: Coat protein]]
-[[Category: core protein]]
+[[Category: Core protein]]
-[[Category: envelope protein]]
+[[Category: Envelope protein]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: helicase]]
+[[Category: Helicase]]
-[[Category: initiation]]
+[[Category: Initiation]]
-[[Category: nonstructural protein hydrolase]]
+[[Category: Nonstructural protein hydrolase]]
-[[Category: polyprotein]]
+[[Category: Polyprotein]]
-[[Category: rna-dependent rna polymerase]]
+[[Category: Rna-dependent rna polymerase]]
-[[Category: rna-directed rna polymerase]]
+[[Category: Rna-directed rna polymerase]]
-[[Category: serine protease]]
+[[Category: Serine protease]]
-[[Category: transferase]]
+[[Category: Transferase]]
-[[Category: transmembrane]]
+[[Category: Transmembrane]]
-[[Category: virus replication]]
+[[Category: Virus replication]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:07:45 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:53:10 2008''