2noa

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:2noa.gif|left|200px]]
[[Image:2noa.gif|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 2noa |SIZE=350|CAPTION= <scene name='initialview01'>2noa</scene>, resolution 1.80&Aring;
+
The line below this paragraph, containing "STRUCTURE_2noa", creates the "Structure Box" on the page.
-
|SITE=
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|LIGAND= <scene name='pdbligand=3TC:4-AMINO-1-[(2R,5S)-2-(HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]PYRIMIDIN-2(1H)-ONE'>3TC</scene>, <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|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>
+
or leave the SCENE parameter empty for the default display.
-
|GENE= DCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
-->
-
|DOMAIN=
+
{{STRUCTURE_2noa| PDB=2noa | SCENE= }}
-
|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=2noa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2noa OCA], [http://www.ebi.ac.uk/pdbsum/2noa PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2noa RCSB]</span>
+
-
}}
+
'''The structure of deoxycytidine kinase complexed with lamivudine and ADP.'''
'''The structure of deoxycytidine kinase complexed with lamivudine and ADP.'''
Line 29: Line 26:
[[Category: Sabini, E.]]
[[Category: Sabini, E.]]
[[Category: 3tc]]
[[Category: 3tc]]
-
[[Category: antiviral]]
+
[[Category: Antiviral]]
-
[[Category: dck]]
+
[[Category: Dck]]
-
[[Category: enantiomer]]
+
[[Category: Enantiomer]]
-
[[Category: epivir]]
+
[[Category: Epivir]]
-
[[Category: human deoxycytidine kinase]]
+
[[Category: Human deoxycytidine kinase]]
-
[[Category: l-dc]]
+
[[Category: L-dc]]
-
[[Category: lamivudine]]
+
[[Category: Lamivudine]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:42:02 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:05:53 2008''
+

Revision as of 06:42, 4 May 2008

Image:2noa.gif

Template:STRUCTURE 2noa

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 May 4 09:42:02 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2noa"
Personal tools