2no6
From Proteopedia
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|PDB= 2no6 |SIZE=350|CAPTION= <scene name='initialview01'>2no6</scene>, resolution 1.90Å | |PDB= 2no6 |SIZE=350|CAPTION= <scene name='initialview01'>2no6</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> | + | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ETV:4-AMINO-5-FLUORO-1-[(2R,5S)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]PYRIMIDIN-2(1H)-ONE'>ETV</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Deoxycytidine_kinase Deoxycytidine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.74 2.7.1.74] </span> |
|GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1p5z|1P5Z]], [[1p60|1P60]], [[1p61|1P61]], [[1p62|1P62]], [[2a2z|2A2Z]], [[2a30|2A30]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2no6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2no6 OCA], [http://www.ebi.ac.uk/pdbsum/2no6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2no6 RCSB]</span> | ||
}} | }} | ||
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[[Category: Lavie, A.]] | [[Category: Lavie, A.]] | ||
[[Category: Sabini, E.]] | [[Category: Sabini, E.]] | ||
| - | [[Category: ADP]] | ||
| - | [[Category: ETV]] | ||
[[Category: antiviral]] | [[Category: antiviral]] | ||
[[Category: dck]] | [[Category: dck]] | ||
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[[Category: human deoxycytidine kinase]] | [[Category: human deoxycytidine kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:05:53 2008'' |
Revision as of 01:05, 31 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | DCK (Homo sapiens) | ||||||
| Activity: | Deoxycytidine kinase, with EC number 2.7.1.74 | ||||||
| Related: | 1P5Z, 1P60, 1P61, 1P62, 2A2Z, 2A30
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
C4S dCK variant of dCK in complex with FTC+ADP
Overview
Biological molecules are predominantly enantioselective. Yet currently two nucleoside analogue prodrugs (3TC and FTC) with opposite chirality compared to physiological nucleosides are clinically approved for the treatment of HIV infections. These prodrugs require conversion to their triphosphorylated forms to achieve pharmacological activity. The first step in the activation of these agents is catalyzed by human deoxycytidine kinase (dCK). This enzyme possesses the ability to phosphorylate nucleosides of the unnatural l-chirality. To understand the molecular basis for the nonenantioselectivity of dCK, we solved the crystal structures of the enzyme in complex with the l-enantiomer and of its physiological substrate deoxycytidine and with the l-nucleoside analogue FTC. These were compared to a structure solved with d-dC. Our results highlight structural adjustments imposed on the l-nucleosides and properties of the enzyme endowing it with the ability to phosphorylate substrates with nonphysiological chirality. This work reveals the molecular basis for the activation of l-nucleosides by dCK.
About this Structure
2NO6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Nonenantioselectivity Property of Human Deoxycytidine Kinase Explained by Structures of the Enzyme in Complex with l- and d-Nucleosides., Sabini E, Hazra S, Konrad M, Lavie A, J Med Chem. 2007 Jun 28;50(13):3004-14. Epub 2007 May 27. PMID:17530837
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