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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.
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