2gv9: Difference between revisions

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[[Image:2gv9.gif|left|200px]]


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==Crystal structure of the Herpes Simplex virus type 1 DNA polymerase==
The line below this paragraph, containing "STRUCTURE_2gv9", creates the "Structure Box" on the page.
<StructureSection load='2gv9' size='340' side='right'caption='[[2gv9]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2gv9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_KOS Human alphaherpesvirus 1 strain KOS]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GV9 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.68&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAI:GUANIDINE'>GAI</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_2gv9| PDB=2gv9 |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gv9 OCA], [https://pdbe.org/2gv9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gv9 RCSB], [https://www.ebi.ac.uk/pdbsum/2gv9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gv9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPOL_HHV1K DPOL_HHV1K] Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication (By similarity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gv/2gv9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gv9 ConSurf].
<div style="clear:both"></div>


'''Crystal structure of the Herpes Simplex virus type 1 DNA polymerase'''
==See Also==
 
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 
__TOC__
==Overview==
</StructureSection>
Herpesviruses are the second leading cause of human viral diseases. Herpes Simplex Virus types 1 and 2 and Varicella-zoster virus produce neurotropic infections such as cutaneous and genital herpes, chickenpox, and shingles. Infections of a lymphotropic nature are caused by cytomegalovirus, HSV-6, HSV-7, and Epstein-Barr virus producing lymphoma, carcinoma, and congenital abnormalities. Yet another series of serious health problems are posed by infections in immunocompromised individuals. Common therapies for herpes viral infections employ nucleoside analogs, such as Acyclovir, and target the viral DNA polymerase, essential for viral DNA replication. Although clinically useful, this class of drugs exhibits a narrow antiviral spectrum, and resistance to these agents is an emerging problem for disease management. A better understanding of herpes virus replication will help the development of new safe and effective broad spectrum anti-herpetic drugs that fill an unmet need. Here, we present the first crystal structure of a herpesvirus polymerase, the Herpes Simplex Virus type 1 DNA polymerase, at 2.7 A resolution. The structural similarity of this polymerase to other alpha polymerases has allowed us to construct high confidence models of a replication complex of the polymerase and of Acyclovir as a DNA chain terminator. We propose a novel inhibition mechanism in which a representative of a series of non-nucleosidic viral polymerase inhibitors, the 4-oxo-dihydroquinolines, binds at the polymerase active site interacting non-covalently with both the polymerase and the DNA duplex.
[[Category: Human alphaherpesvirus 1 strain KOS]]
 
[[Category: Large Structures]]
==About this Structure==
[[Category: Liu S]]
2GV9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_1 Human herpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GV9 OCA].
 
==Reference==
Crystal structure of the herpes simplex virus 1 DNA polymerase., Liu S, Knafels JD, Chang JS, Waszak GA, Baldwin ET, Deibel MR Jr, Thomsen DR, Homa FL, Wells PA, Tory MC, Poorman RA, Gao H, Qiu X, Seddon AP, J Biol Chem. 2006 Jun 30;281(26):18193-200. Epub 2006 Apr 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16638752 16638752]
[[Category: DNA-directed DNA polymerase]]
[[Category: Human herpesvirus 1]]
[[Category: Single protein]]
[[Category: Liu, S.]]
[[Category: Polymerase alpha fold]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:34:51 2008''

Latest revision as of 12:30, 14 February 2024

Crystal structure of the Herpes Simplex virus type 1 DNA polymeraseCrystal structure of the Herpes Simplex virus type 1 DNA polymerase

Structural highlights

2gv9 is a 2 chain structure with sequence from Human alphaherpesvirus 1 strain KOS. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.68Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPOL_HHV1K Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2gv9, resolution 2.68Å

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