2cko: Difference between revisions
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|SITE= <scene name='pdbsite=AC1:Dtt+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Dtt+Binding+Site+For+Chain+B'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene> | |LIGAND= <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Choline_kinase Choline kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.32 2.7.1.32] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Choline_kinase Choline kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.32 2.7.1.32] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cko OCA], [http://www.ebi.ac.uk/pdbsum/2cko PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2cko RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Choline kinase, responsible for the phosphorylation of choline to phosphocholine as the first step of the CDP-choline pathway for the biosynthesis of phosphatidylcholine, has been recognized as a new target for anticancer therapy. Crystal structures of human choline kinase in its apo, ADP and phosphocholine-bound complexes, respectively, reveal the molecular details of the substrate binding sites. ATP binds in a cavity where residues from both the N and C-terminal lobes contribute to form a cleft, while the choline-binding site constitutes a deep hydrophobic groove in the C-terminal domain with a rim composed of negatively charged residues. Upon binding of choline, the enzyme undergoes conformational changes independently affecting the N-terminal domain and the ATP-binding loop. From this structural analysis and comparison with other kinases, and from mutagenesis data on the homologous Caenorhabditis elegans choline kinase, a model of the ternary ADP.phosphocholine complex was built that reveals the molecular basis for the phosphoryl transfer activity of this enzyme. | Choline kinase, responsible for the phosphorylation of choline to phosphocholine as the first step of the CDP-choline pathway for the biosynthesis of phosphatidylcholine, has been recognized as a new target for anticancer therapy. Crystal structures of human choline kinase in its apo, ADP and phosphocholine-bound complexes, respectively, reveal the molecular details of the substrate binding sites. ATP binds in a cavity where residues from both the N and C-terminal lobes contribute to form a cleft, while the choline-binding site constitutes a deep hydrophobic groove in the C-terminal domain with a rim composed of negatively charged residues. Upon binding of choline, the enzyme undergoes conformational changes independently affecting the N-terminal domain and the ATP-binding loop. From this structural analysis and comparison with other kinases, and from mutagenesis data on the homologous Caenorhabditis elegans choline kinase, a model of the ternary ADP.phosphocholine complex was built that reveals the molecular basis for the phosphoryl transfer activity of this enzyme. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Lavie, A.]] | [[Category: Lavie, A.]] | ||
[[Category: Malito, E.]] | [[Category: Malito, E.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: choline kinase]] | [[Category: choline kinase]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''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 02:22:50 2008'' | ||
