NMR structural characterization of the penta-peptide calpain inhibitor.
Calpains are ubiquitous intracellular calcium- and thiol-dependent proteases. Their over activation, resulting in the degradation of various substrates, has been implicated in a number of cardiovascular and neurological disorders. Here, we present the first structural characterization of LSEAL penta-peptide, a potent calpain inhibitor, bound to the calmodulin-like domain of calpain. Our in vitro binding data supports the idea that domains other than calpain's active site may be suitable targets for future development of therapeutic agents to be used to treat heart attack, traumatic brain injuries or a variety of neurodegenerative conditions, such as ischemic stroke.
Deshmukh
Lalit
L
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269-3092, USA.
Wu
Liping
L
Guttmann
Rodney P
RP
Vinogradova
Olga
O
D000595:Amino Acid Sequence; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation
D002147:Calmodulin; D006023:Glycoproteins; C503415:Leu-Ser-Glu-Ala-Leu; D009842:Oligopeptides; C039304:calpain inhibitors