2no9: Difference between revisions
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[[Image:2no9.gif|left|200px]] | [[Image:2no9.gif|left|200px]] | ||
'''The structure of deoxycytidine kinase complexed with troxacitabine and ADP.''' | {{Structure | ||
|PDB= 2no9 |SIZE=350|CAPTION= <scene name='initialview01'>2no9</scene>, resolution 2.15Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> and <scene name='pdbligand=LTT:4-AMINO-1-[(2S,4S)-2-(HYDROXYMETHYL)-1,3-DIOXOLAN-4-YL]PYRIMIDIN-2(1H)-ONE'>LTT</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] | |||
|GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''The structure of deoxycytidine kinase complexed with troxacitabine and ADP.''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2NO9 is a [ | 2NO9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NO9 OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase., Sabini E, Hazra S, Konrad M, Burley SK, Lavie A, Nucleic Acids Res. 2007;35(1):186-92. Epub 2006 Dec 7. PMID:[http:// | Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase., Sabini E, Hazra S, Konrad M, Burley SK, Lavie A, Nucleic Acids Res. 2007;35(1):186-92. Epub 2006 Dec 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17158155 17158155] | ||
[[Category: Deoxycytidine kinase]] | [[Category: Deoxycytidine kinase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: troxacitabine]] | [[Category: troxacitabine]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:48:55 2008'' | ||
Revision as of 15:49, 20 March 2008
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| 2no9, resolution 2.15Å | |||||||||||||
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| Ligands: | ADP and LTT | ||||||||||||
| Gene: | DCK (Homo sapiens) | ||||||||||||
| Activity: | Deoxycytidine kinase, with EC number 2.7.1.74 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
The structure of deoxycytidine kinase complexed with troxacitabine and ADP.
Overview
L-nucleoside analogs represent an important class of small molecules for treating both viral infections and cancers. These pro-drugs achieve pharmacological activity only after enzyme-catalyzed conversion to their tri-phosphorylated forms. Herein, we report the crystal structures of human deoxycytidine kinase (dCK) in complex with the L-nucleosides (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC)--an approved anti-human immunodeficiency virus (HIV) agent--and troxacitabine (TRO)--an experimental anti-neoplastic agent. The first step in activating these agents is catalyzed by dCK. Our studies reveal how dCK, which normally catalyzes phosphorylation of the natural D-nucleosides, can efficiently phosphorylate substrates with non-physiologic chirality. The capability of dCK to phosphorylate both D- and L-nucleosides and nucleoside analogs derives from structural properties of both the enzyme and the substrates themselves. First, the nucleoside-binding site tolerates substrates with different chiral configurations by maintaining virtually all of the protein-ligand interactions responsible for productive substrate positioning. Second, the pseudo-symmetry of nucleosides and nucleoside analogs in combination with their conformational flexibility allows the L- and D-enantiomeric forms to adopt similar shapes when bound to the enzyme. This is the first analysis of the structural basis for activation of L-nucleoside analogs, providing further impetus for discovery and clinical development of new agents in this molecular class.
About this Structure
2NO9 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for activation of the therapeutic L-nucleoside analogs 3TC and troxacitabine by human deoxycytidine kinase., Sabini E, Hazra S, Konrad M, Burley SK, Lavie A, Nucleic Acids Res. 2007;35(1):186-92. Epub 2006 Dec 7. PMID:17158155
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