2ckp: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==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, ... | 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== | ||
2CKP is a | 2CKP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ADP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CKP OCA]. | ||
==Reference== | ==Reference== | ||
| Line 24: | Line 24: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:35:41 2007'' | ||
