1vtk
From Proteopedia
(New page: 200px<br /><applet load="1vtk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vtk, resolution 2.75Å" /> '''THYMIDINE KINASE FRO...) |
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| - | [[Image:1vtk.jpg|left|200px]]<br /><applet load="1vtk" size=" | + | [[Image:1vtk.jpg|left|200px]]<br /><applet load="1vtk" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1vtk, resolution 2.75Å" /> | caption="1vtk, resolution 2.75Å" /> | ||
'''THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE 1 IN COMPLEX WITH ADP AND DEOXYTHYMIDINE-MONOPHOSPHATE'''<br /> | '''THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE 1 IN COMPLEX WITH ADP AND DEOXYTHYMIDINE-MONOPHOSPHATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Thymidine kinase from Herpes simplex virus type 1 (TK) was crystallized in | + | Thymidine kinase from Herpes simplex virus type 1 (TK) was crystallized in an N-terminally truncated but fully active form. The structures of TK complexed with ADP at the ATP-site and deoxythymidine-5'-monophosphate (dTMP), deoxythymidine (dT), or idoxuridine-5'-phosphate (5-iodo-dUMP) at the substrate-site were refined to 2.75 A, 2.8 A, and 3.0 A resolution, respectively. TK catalyzes the phosphorylation of dT resulting in an ester, and the phosphorylation of dTMP giving rise to an anhydride. The presented TK structures indicate that there are only small differences between these two modes of action. Glu83 serves as a general base in the ester reaction. Arg163 parks at an internal aspartate during ester formation and binds the alpha-phosphate of dTMP during anhydride formation. The bound deoxythymidine leaves a 35 A3 cavity at position 5 of the base and two sequestered water molecules at position 2. Cavity and water molecules reduce the substrate specificity to such an extent that TK can phosphorylate various substrate analogues useful in pharmaceutical applications. TK is structurally homologous to the well-known nucleoside monophosphate kinases but contains large additional peptide segments. |
==About this Structure== | ==About this Structure== | ||
| - | 1VTK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4] with ADP and TMP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.21 2.7.1.21] Full crystallographic information is available from [http:// | + | 1VTK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4] with <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=TMP:'>TMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thymidine_kinase Thymidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.21 2.7.1.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VTK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thymidine kinase]] | [[Category: Thymidine kinase]] | ||
| - | [[Category: Schulz, G | + | [[Category: Schulz, G E.]] |
[[Category: Wild, K.]] | [[Category: Wild, K.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:38:17 2008'' |
Revision as of 13:38, 21 February 2008
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THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE 1 IN COMPLEX WITH ADP AND DEOXYTHYMIDINE-MONOPHOSPHATE
Overview
Thymidine kinase from Herpes simplex virus type 1 (TK) was crystallized in an N-terminally truncated but fully active form. The structures of TK complexed with ADP at the ATP-site and deoxythymidine-5'-monophosphate (dTMP), deoxythymidine (dT), or idoxuridine-5'-phosphate (5-iodo-dUMP) at the substrate-site were refined to 2.75 A, 2.8 A, and 3.0 A resolution, respectively. TK catalyzes the phosphorylation of dT resulting in an ester, and the phosphorylation of dTMP giving rise to an anhydride. The presented TK structures indicate that there are only small differences between these two modes of action. Glu83 serves as a general base in the ester reaction. Arg163 parks at an internal aspartate during ester formation and binds the alpha-phosphate of dTMP during anhydride formation. The bound deoxythymidine leaves a 35 A3 cavity at position 5 of the base and two sequestered water molecules at position 2. Cavity and water molecules reduce the substrate specificity to such an extent that TK can phosphorylate various substrate analogues useful in pharmaceutical applications. TK is structurally homologous to the well-known nucleoside monophosphate kinases but contains large additional peptide segments.
About this Structure
1VTK is a Single protein structure of sequence from Human herpesvirus 4 with and as ligands. Active as Thymidine kinase, with EC number 2.7.1.21 Full crystallographic information is available from OCA.
Reference
The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue., Wild K, Bohner T, Folkers G, Schulz GE, Protein Sci. 1997 Oct;6(10):2097-106. PMID:9336833
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