Defining the binding site of levosimendan and its analogues in a regulatory cardiac troponin C-troponin I complex.

ABSTRACT: The interaction of Cardiac Troponin C (cTnC) and Cardiac Troponin I (cTnI) plays a critical role in transmitting the Ca (2+) signal to the other myofilament proteins in the activation of cardiac muscle contraction. As such, the cTnC-cTnI interface is a logical target for cardiotonic agents such as levosimendan that can modulate the Ca (2+) sensitivity of the myofilaments. Evidence indicates that drug candidates may exert their effects by targeting a site formed by binding of the switch region of cTnI to the regulatory N domain of cTnC (cNTnC). In this study, we utilized two-dimensional (1)H- (15)N HSQC NMR spectroscopy to monitor the binding of levosimendan and its analogues, CMDP, AMDP, CI-930, imazodan, and MPDP, to cNTnC.Ca (2+) in complex with two versions of the switch region of cTnI

SUBMITTER: Robertson IM 

PROVIDER: S-EPMC2652250 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature