1xa5: Difference between revisions
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[[Image:1xa5.gif|left|200px]] | [[Image:1xa5.gif|left|200px]] | ||
'''Structure of Calmodulin in complex with KAR-2, a bis-indol alkaloid''' | {{Structure | ||
|PDB= 1xa5 |SIZE=350|CAPTION= <scene name='initialview01'>1xa5</scene>, resolution 2.12Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=KAR:3 -(BETA-CHLOROETHYL)-2 ,4 -DIOXO-3, 5 -SPIRO-OXAZOLIDINO-4-DEACETOXY-VINBLASTINE'>KAR</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''Structure of Calmodulin in complex with KAR-2, a bis-indol alkaloid''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1XA5 is a [ | 1XA5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XA5 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15596444 15596444] | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: vinca alkaloid]] | [[Category: vinca alkaloid]] | ||
''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 15:07:07 2008'' | ||
Revision as of 16:07, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Calmodulin in complex with KAR-2, a bis-indol alkaloid
OverviewOverview
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 StructureAbout this Structure
1XA5 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
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
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