1xa5
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1xa5 |SIZE=350|CAPTION= <scene name='initialview01'>1xa5</scene>, resolution 2.12Å | |PDB= 1xa5 |SIZE=350|CAPTION= <scene name='initialview01'>1xa5</scene>, resolution 2.12Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=KAR:3"-(BETA-CHLOROETHYL)-2",4"-DIOXO-3,+5"-SPIRO-OXAZOLIDINO-4-DEACETOXY-VINBLASTINE'>KAR</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xa5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xa5 OCA], [http://www.ebi.ac.uk/pdbsum/1xa5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xa5 RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Naray-Szabo, G.]] | [[Category: Naray-Szabo, G.]] | ||
[[Category: Ovadi, J.]] | [[Category: Ovadi, J.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: KAR]] | ||
[[Category: calmodulin]] | [[Category: calmodulin]] | ||
[[Category: drug binding]] | [[Category: drug binding]] | ||
| Line 34: | Line 35: | ||
[[Category: vinca alkaloid]] | [[Category: vinca alkaloid]] | ||
| - | ''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 00:46:54 2008'' |
Revision as of 21:46, 30 March 2008
| |||||||
| , resolution 2.12Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Calmodulin in complex with KAR-2, a bis-indol alkaloid
Overview
3'-(beta-Chloroethyl)-2',4'-dioxo-3,5'-spiro-oxazolidino-4-deacetoxyvinbla stine (KAR-2) is a potent anti-microtubular agent that arrests mitosis in cancer cells without significant toxic side effects. In this study we demonstrate that in addition to targeting microtubules, KAR-2 also binds calmodulin, thereby countering the antagonistic effects of trifluoperazine. To determine the basis of both properties of KAR-2, the three-dimensional structure of its complex with Ca(2+)-calmodulin has been characterized both in solution using NMR and when crystallized using x-ray diffraction. Heterocorrelation ((1)H-(15)N heteronuclear single quantum coherence) spectra of (15)N-labeled calmodulin indicate a global conformation change (closure) of the protein upon its binding to KAR-2. The crystal structure at 2.12-A resolution reveals a more complete picture; KAR-2 binds to a novel structure created by amino acid residues of both the N- and C-terminal domains of calmodulin. Although first detected by x-ray diffraction of the crystallized ternary complex, this conformational change is consistent with its solution structure as characterized by NMR spectroscopy. It is noteworthy that a similar tertiary complex forms when calmodulin binds KAR-2 as when it binds trifluoperazine, even though the two ligands contact (for the most part) different amino acid residues. These observations explain the specificity of KAR-2 as an anti-microtubular agent; the drug interacts with a novel drug binding domain on calmodulin. Consequently, KAR-2 does not prevent calmodulin from binding most of its physiological targets.
About this Structure
1XA5 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
The structure of the complex of calmodulin with KAR-2: a novel mode of binding explains the unique pharmacology of the drug., Horvath I, Harmat V, Perczel A, Palfi V, Nyitray L, Nagy A, Hlavanda E, Naray-Szabo G, Ovadi J, J Biol Chem. 2005 Mar 4;280(9):8266-74. Epub 2004 Dec 13. PMID:15596444
Page seeded by OCA on Mon Mar 31 00:46:54 2008
