2noa
From Proteopedia
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|PDB= 2noa |SIZE=350|CAPTION= <scene name='initialview01'>2noa</scene>, resolution 1.80Å | |PDB= 2noa |SIZE=350|CAPTION= <scene name='initialview01'>2noa</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5 | + | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> and <scene name='pdbligand=3TC:4-AMINO-1-[(2R,5S)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]PYRIMIDIN-2(1H)-ONE'>3TC</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= [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]) | |GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
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[[Category: lamivudine]] | [[Category: lamivudine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:28:14 2008'' |
Revision as of 13:28, 23 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| 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 lamivudine 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
2NOA 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
Page seeded by OCA on Sun Mar 23 15:28:14 2008
Categories: Deoxycytidine kinase | Homo sapiens | Single protein | Lavie, A. | Sabini, E. | 3TC | ADP | 3tc | Antiviral | Dck | Enantiomer | Epivir | Human deoxycytidine kinase | L-dc | Lamivudine
