1ki6
From Proteopedia
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|PDB= 1ki6 |SIZE=350|CAPTION= <scene name='initialview01'>1ki6</scene>, resolution 2.37Å | |PDB= 1ki6 |SIZE=350|CAPTION= <scene name='initialview01'>1ki6</scene>, resolution 2.37Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=AHU:1',5'-ANHYDRO-2',3'-DIDEOXY-2'-(5-IODOURACIL-1-YL)-D-ABABINO-HEXITOL'>AHU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
| - | |GENE= TK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | + | |GENE= TK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10298 Human herpesvirus 1]) |
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ki6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ki6 OCA], [http://www.ebi.ac.uk/pdbsum/1ki6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ki6 RCSB]</span> | ||
}} | }} | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KI6 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ | + | 1KI6 is a [[Protein complex]] structure of sequences 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=1KI6 OCA]. |
==Reference== | ==Reference== | ||
Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands., Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR, Proteins. 1998 Aug 15;32(3):350-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9715911 9715911] | Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands., Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR, Proteins. 1998 Aug 15;32(3):350-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9715911 9715911] | ||
| - | [[Category: Human herpesvirus | + | [[Category: Human herpesvirus 1]] |
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thymidine kinase]] | [[Category: Thymidine kinase]] | ||
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[[Category: Summers, W C.]] | [[Category: Summers, W C.]] | ||
[[Category: Wien, F.]] | [[Category: Wien, F.]] | ||
| - | [[Category: AHU]] | ||
| - | [[Category: SO4]] | ||
[[Category: 5-iodouracil anhydrohexitol nucleoside]] | [[Category: 5-iodouracil anhydrohexitol nucleoside]] | ||
[[Category: alphaherpesvirinae]] | [[Category: alphaherpesvirinae]] | ||
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[[Category: viridae]] | [[Category: viridae]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:48:56 2008'' |
Revision as of 18:48, 30 March 2008
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| , resolution 2.37Å | |||||||
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| Ligands: | , | ||||||
| Gene: | TK (Human herpesvirus 1) | ||||||
| Activity: | Thymidine kinase, with EC number 2.7.1.21 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE I COMPLEXED WITH A 5-IODOURACIL ANHYDROHEXITOL NUCLEOSIDE
Overview
Antiherpes therapies are principally targeted at viral thymidine kinases and utilize nucleoside analogs, the triphosphates of which are inhibitors of viral DNA polymerase or result in toxic effects when incorporated into DNA. The most frequently used drug, aciclovir (Zovirax), is a relatively poor substrate for thymidine kinase and high-resolution structural information on drugs and other molecules binding to the target is therefore important for the design of novel and more potent chemotherapy, both in antiherpes treatment and in gene therapy systems where thymidine kinase is expressed. Here, we report for the first time the binary complexes of HSV-1 thymidine kinase (TK) with the drug molecules aciclovir and penciclovir, determined by X-ray crystallography at 2.37 A resolution. Moreover, from new data at 2.14 A resolution, the refined structure of the complex of TK with its substrate deoxythymidine (R = 0.209 for 96% of all data) now reveals much detail concerning substrate and solvent interactions with the enzyme. Structures of the complexes of TK with four halogen-containing substrate analogs have also been solved, to resolutions better than 2.4 A. The various TK inhibitors broadly fall into three groups which together probe the space of the enzyme active site in a manner that no one molecule does alone, so giving a composite picture of active site interactions that can be exploited in the design of novel compounds.
About this Structure
1KI6 is a Protein complex structure of sequences from Human herpesvirus 1. Full crystallographic information is available from OCA.
Reference
Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands., Champness JN, Bennett MS, Wien F, Visse R, Summers WC, Herdewijn P, de Clerq E, Ostrowski T, Jarvest RL, Sanderson MR, Proteins. 1998 Aug 15;32(3):350-61. PMID:9715911
Page seeded by OCA on Sun Mar 30 21:48:56 2008
Categories: Human herpesvirus 1 | Protein complex | Thymidine kinase | Bennett, M S. | Champness, J N. | Herdewijn, P. | Ostrowski, T. | Sanderson, M R. | Summers, W C. | Wien, F. | 5-iodouracil anhydrohexitol nucleoside | Alphaherpesvirinae | Ds-dna enveloped viruse | Herpesviridae | Phosphotransferase | Substrate analog | Viridae
