2a7q
From Proteopedia
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| - | [[Image:2a7q.gif|left|200px]] | + | [[Image:2a7q.gif|left|200px]] |
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| - | '''Crystal structure of human dCK complexed with clofarabine and ADP''' | + | {{Structure |
| + | |PDB= 2a7q |SIZE=350|CAPTION= <scene name='initialview01'>2a7q</scene>, resolution 2.55Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> and <scene name='pdbligand=CFB:2-CHLORO-9-(2-DEOXY-2-FLUORO-B -D-ARABINOFURANOSYL)-9H-PURIN-6-AMINE'>CFB</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]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of human dCK complexed with clofarabine and ADP''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2A7Q is a [ | + | 2A7Q 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=2A7Q OCA]. |
==Reference== | ==Reference== | ||
| - | The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation., Zhang Y, Secrist JA 3rd, Ealick SE, Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):133-9. Epub 2006, Jan 18. PMID:[http:// | + | The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation., Zhang Y, Secrist JA 3rd, Ealick SE, Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):133-9. Epub 2006, Jan 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16421443 16421443] |
[[Category: Deoxycytidine kinase]] | [[Category: Deoxycytidine kinase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: CFB]] | [[Category: CFB]] | ||
[[Category: MG]] | [[Category: MG]] | ||
| - | [[Category: alpha/beta parallel beta-sheet of 5 | + | [[Category: alpha/beta parallel beta-sheet of 5 strand]] |
| - | ''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 15:46:23 2008'' |
Revision as of 13:46, 20 March 2008
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| , resolution 2.55Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | DCK (Homo sapiens) | ||||||
| Activity: | Deoxycytidine kinase, with EC number 2.7.1.74 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human dCK complexed with clofarabine and ADP
Overview
Clofarabine [2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine] is a hybrid of the widely used anticancer drugs cladribine and fludarabine. It is the precursor of an effective chemotherapeutic agent for leukemias and other hematological malignancies and received accelerated approval by the FDA for the treatment of pediatric patients with relapsed or refractory acute lymphoblastic leukemia. Clofarabine is phosphorylated intracellularly by human deoxycytidine kinase (dCK) to the 5'-monophosphate, which is the rate-limiting step in activation of the prodrug. dCK has a broad substrate specificity, with a much higher activity to deoxycytidine than to deoxyadenosine and deoxyguanosine. As a purine-nucleoside analog, clofarabine is a better substrate of dCK than deoxycytidine. The crystal structure of dCK has been solved previously in complex with pyrimidine nucleosides and ADP [Sabini et al. (2003), Nature Struct. Biol. 10, 513-519]. In the current study, the crystal structure of clofarabine- and ADP-bound dCK was solved to 2.55 angstroms by molecular replacement. It appears that the enzyme takes the same conformation as in the structures of the pyrimidine nucleoside-bound complexes. The interactions between 2-Cl and its surrounding hydrophobic residues contribute to the high catalytic efficiency of dCK for clofarabine.
About this Structure
2A7Q is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activation., Zhang Y, Secrist JA 3rd, Ealick SE, Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):133-9. Epub 2006, Jan 18. PMID:16421443
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