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| {{STRUCTURE_1e2h| PDB=1e2h | SCENE= }} | | {{STRUCTURE_1e2h| PDB=1e2h | SCENE= }} |
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| '''THE NUCLEOSIDE BINDING SITE OF HERPES SIMPLEX TYPE 1 THYMIDINE KINASE ANALYZED BY X-RAY CRYSTALLOGRAPHY'''
| | ===THE NUCLEOSIDE BINDING SITE OF HERPES SIMPLEX TYPE 1 THYMIDINE KINASE ANALYZED BY X-RAY CRYSTALLOGRAPHY=== |
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| ==Overview==
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| The crystal structures of the full-length Herpes simplex virus type 1 thymidine kinase in its unligated form and in a complex with an adenine analogue have been determined at 1.9 A resolution. The unligated enzyme contains four water molecules in the thymidine pocket and reveals a small induced fit on substrate binding. The structure of the ligated enzyme shows for the first time a bound adenine analogue after numerous complexes with thymine and guanine analogues have been reported. The adenine analogue constitutes a new lead compound for enzyme-prodrug gene therapy. In addition, the structure of mutant Q125N modifying the binding site of the natural substrate thymidine in complex with this substrate has been established at 2.5 A resolution. It reveals that neither the binding mode of thymidine nor the polypeptide backbone conformation is altered, except that the two major hydrogen bonds to thymidine are replaced by a single water-mediated hydrogen bond, which improves the relative acceptance of the prodrugs aciclovir and ganciclovir compared with the natural substrate. Accordingly, the mutant structure represents a first step toward improving the virus-directed enzyme-prodrug gene therapy by enzyme engineering. | | The line below this paragraph, {{ABSTRACT_PUBMED_11056041}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11056041 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11056041}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Thymidine kinase]] | | [[Category: Thymidine kinase]] |
| [[Category: X-ray crystallography]] | | [[Category: X-ray crystallography]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:34:37 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 00:02:23 2008'' |
