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2gv9

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{{STRUCTURE_2gv9| PDB=2gv9 | SCENE= }}
{{STRUCTURE_2gv9| PDB=2gv9 | SCENE= }}
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'''Crystal structure of the Herpes Simplex virus type 1 DNA polymerase'''
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===Crystal structure of the Herpes Simplex virus type 1 DNA polymerase===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16638752 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16638752}}
==About this Structure==
==About this Structure==
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[[Category: Liu, S.]]
[[Category: Liu, S.]]
[[Category: Polymerase alpha fold]]
[[Category: Polymerase alpha fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:56:39 2008''

Revision as of 17:56, 27 July 2008

Image:2gv9.png

Template:STRUCTURE 2gv9

Crystal structure of the Herpes Simplex virus type 1 DNA polymerase

Template:ABSTRACT PUBMED 16638752

About this Structure

2GV9 is a Single protein structure of sequence from Human herpesvirus 1. Full crystallographic information is available from 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:16638752

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