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Crystallization and preliminary diffraction analysis of Ca 2+ ‐calmodulin‐drug and apocalmodulin‐drug complexes
Author(s) -
Vertessy Beata G.,
Böcskei Zsolt,
Harmath Veronika,
NáraySzabó Gábor,
Ovádi Judit
Publication year - 1997
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199705)28:1<131::aid-prot13>3.0.co;2-k
Subject(s) - drug , calmodulin , crystallization , pharmacology , chemistry , calcium , medicine , organic chemistry
Ca 2+ ‐calmodulin is crystallized with two new and potent drugs: a bisindol derivative (KAR‐2, 3”‐(β‐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 Å 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 Å 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. © 1997 Wiley‐Liss Inc.