1w4r

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==Overview==
==Overview==
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The structure of human cytosolic thymidine kinase in complex with its, feedback inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This, structure is the first representative of the type II thymidine kinases, found in several pathogens. The structure deviates strongly from the known, structures of type I thymidine kinases such as the Herpes simplex enzyme., It contains a zinc-binding domain with four cysteines complexing a, structural zinc ion. Interestingly, the backbone atoms of the type II, enzyme bind thymine via hydrogen-bonds, in contrast to type I, where side, chains are involved. This results in a specificity difference exploited, for antiviral therapy. The presented structure will foster the development, of new drugs and prodrugs for numerous therapeutic applications.
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The structure of human cytosolic thymidine kinase in complex with its feedback inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This structure is the first representative of the type II thymidine kinases found in several pathogens. The structure deviates strongly from the known structures of type I thymidine kinases such as the Herpes simplex enzyme. It contains a zinc-binding domain with four cysteines complexing a structural zinc ion. Interestingly, the backbone atoms of the type II enzyme bind thymine via hydrogen-bonds, in contrast to type I, where side chains are involved. This results in a specificity difference exploited for antiviral therapy. The presented structure will foster the development of new drugs and prodrugs for numerous therapeutic applications.
==About this Structure==
==About this Structure==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Thymidine kinase]]
[[Category: Thymidine kinase]]
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[[Category: Birringer, M.S.]]
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[[Category: Birringer, M S.]]
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[[Category: Claus, M.T.]]
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[[Category: Claus, M T.]]
[[Category: Folkers, G.]]
[[Category: Folkers, G.]]
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[[Category: Kloer, D.P.]]
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[[Category: Kloer, D P.]]
[[Category: Scapozza, L.]]
[[Category: Scapozza, L.]]
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[[Category: Schulz, G.E.]]
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[[Category: Schulz, G E.]]
[[Category: DTU]]
[[Category: DTU]]
[[Category: TTP]]
[[Category: TTP]]
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[[Category: type ii]]
[[Category: type ii]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:19:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:27 2008''

Revision as of 13:40, 21 February 2008


1w4r, resolution 1.83Å

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STRUCTURE OF A TYPE II THYMIDINE KINASE WITH BOUND DTTP

Overview

The structure of human cytosolic thymidine kinase in complex with its feedback inhibitor 2'-deoxythymidine-5'-triphosphate was determined. This structure is the first representative of the type II thymidine kinases found in several pathogens. The structure deviates strongly from the known structures of type I thymidine kinases such as the Herpes simplex enzyme. It contains a zinc-binding domain with four cysteines complexing a structural zinc ion. Interestingly, the backbone atoms of the type II enzyme bind thymine via hydrogen-bonds, in contrast to type I, where side chains are involved. This results in a specificity difference exploited for antiviral therapy. The presented structure will foster the development of new drugs and prodrugs for numerous therapeutic applications.

About this Structure

1W4R is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of a type II thymidine kinase with bound dTTP., Birringer MS, Claus MT, Folkers G, Kloer DP, Schulz GE, Scapozza L, FEBS Lett. 2005 Feb 28;579(6):1376-82. PMID:15733844

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