Here we show that, as a consequence of binding the drug trifluoperazine, a major conformational movement occurs in Ca(2+)-calmodulin (CaM). The tertiary structure changes from an elongated dumb-bell, with exposed hydrophobic surfaces, to a compact globular form which can no longer interact with its target enzymes. It is likely that inactivation of Ca(2+)-CaM by trifluoperazine is due to this major tertiary-structural alteration in Ca(2+)-CaM, which is initiated and stabilized by drug binding. This conformational change is similar to that which occurs on the binding of Ca(2+)-CaM to target peptides. Two hydrophobic binding pockets, created by amino acid residues adjacent to Ca(2+)-coordinating residues, form the key recognition sites on Ca(2+)-CaM for both inhibitors and target enzymes.

. Can. J. Chem. 58,631 (1980). Nuclear magnetic resonance properties are shown to be in good accord with those that are expected for synthetic oligosaccharides in the conformations which are predicted by hard-sphere molecular modelling and taking into consideration the important contribution by the exa-anomeric effect. The studies involve first a comparison of the PDG~I(IA~)PDGICNAC (Type I) and p~G a l - On montre que les proprietes de rmn sont en accord avec celles attendues pour les oligosaccharides synthetiques selon les conformations prevues par les modeles spheriques rigides et en tenant compte de la contribution importante de l'effet anomkrique eso. Les etudes impliquent en premier lieu une comparaison des structures des disaccharides ~~Gal(1+3)puGlcNAc (type 1) et p~G a l ( 1 4 4 ) P DGIcNAc (type 2) basee principalement sur les donnees de la rmn du I3C et en second lieu I'ttude des relations existant entre les conformations calc~llees et ies parametres de la rmn du lH et du 13C des determinants du groupe sanguin humain qui derivent du noyau disaccharide de type 1. Parmi les structures examinees on trouve le di, tri et tetrasaccharides pour le ABH et les dtterminants antigeniques de Lewis. On note certaines relations immunologiques-conformationnelles.[Traduit par le journal]

Understanding how phosphoryl transfer is accomplished by kinases, a ubiquitous group of enzymes, is central to many biochemical processes. Qualitative analysis of the crystal structures of enzyme-substrate complexes of kinases reveals structural features of these enzymes important to phosphoryl transfer. Recently determined crystal structures which mimic the transition state complex have added new insight into the debate as to whether kinases use associative or dissociative mechanisms of catalysis.

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