title: Crystallization and preliminary diffraction analysis of Ca(2+)-calmodulin-drug and apocalmodulin-drug complexes.
abstract: Ca(2+)-calmodulin is crystallized with two new and potent drugs: a bisindol derivative (KAR-2, 3"-(beta-chloroethyl)-2",4"-dioxo-3,5"- spiro-oxazolidino-4-deacetoxy-vinblastine) with antitumor activity and an arylalkylamine fendiline analogue (N-(3,3-diphenylpropyl)-N'-[1-(3,4- di-n-butoxy-phenyl)-ethyl]-1,3-diaminopropane) with anticalmodulin activity. The crystals diffract beyond 2.8 A and differ in unit cell parameters from each other as well as from crystals of Ca(2+)-calmodulin or Ca(2+)-calmodulin-ligand complexes, as reported thus far. Attempts to crystallize Ca(2+)-free calmodulin without drugs failed, in consonance with earlier results; however, single Ca(2+)-free calmodulin crystals diffracting-beyond 2.5 A resolution were grown in the presence of KAR-2. Results indicate that binding of the two drugs to apocalmodulin or Ca(2+)-calmodulin may induce unique novel protein conformers, targets of further detailed X-ray studies.
authors.affiliation: Institute of Enzymology, Hungarian Academy of Science, Budapest Hungary. vertessy@enzim.hu
authors.forename: B G
authors.initials: BG
authors.lastname: Vertessy
authors.forename: Z
authors.initials: Z
authors.lastname: Böcskei
authors.forename: V
authors.initials: V
authors.lastname: Harmath
authors.forename: G
authors.initials: G
authors.lastname: Náray-Szabó
authors.forename: J
authors.initials: J
authors.lastname: Ovádi
mesh_terms: D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D003460:Crystallization; D005275:Fendiline / Q000031:analogs & derivatives / Q000378:metabolism; D014747:Vinblastine / Q000031:analogs & derivatives / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D002147:Calmodulin; D014747:Vinblastine; D005275:Fendiline; D002118:Calcium