Enhanced Binding and Antagonism of Camstatin



Camstatin is a similar PEP-19 analogue with enhanced calmodulin binding and antagonism. It is a functional 25-residue fragment of the IQ motif of PEP19 that binds to calmodulin and inhibits nitric oxide synthase in neurons. It defines the lowest active domain of PEP-19, and its binding affinity to calmodulin is positively correlated with its role as an inhibitor of nitric oxide synthase.

Pharmacologic action

Calcium ion is one of the most common intracellular second messengers, and uncontrollable increases in intracellular free calcium can lead to neuronal damage and death. Many of the harmful effects of calcium are mediated by calmodulin. Calmodulin can alter the properties of other proteins in calcium binding state. Many of these proteins themselves are part of the signal cascade, involving different neuronal functions. Dose-dependent interactions between Ca2+ and calmodulin lead to robust conformational changes that expose hidden hydrophobic domains required for subsequent action on downstream protein targets. Ca2+ calmodulin complex is formed when Ca2+ enters the cytoplasm, resulting in the increase of intracellular free calcium [Ca2+] I. The conserved polypeptide motifs of Camstatin PEP-19, neurogranulin and neuromodulatory protein can promote the separation of calmodulin from calmodulin, block the interaction with downstream targets, thus regulating intracellular calcium concentration and preventing neuronal injury and death.


Camstatin is an active 25-residue fragment in the IQ motif of PEP-19, which binds to calmodulin and inhibits nitric oxide synthase in neurons. It has enhanced binding and antagonistic effects. It is a calmodulin peptide antagonist based on the conserved structural motif of PEP-19, Neurogranin and Neuromodulin. At present, PEP-19 is mainly used as the smallest active alternative to enzyme inhibition and calmodulin binding sequence requirements, as well as to explore the relationship between PEP-19 as a neuromodulatory protein and various neurological diseases. It has not been fully tested and can not be used for human or veterinary purposes. At present, it is only used for scientific research.


Slemmon J R, Morgan J I, Fullerton S M, et al. Camstatins are peptide antagonists of calmodulin based upon a conserved structural motif in PEP-19, neurogranin, and neuromodulin.[J]. Journal of Biological Chemistry, 1996, 271(27):15911-15917.

Oláh Z, Jósvay K, Pecze L, et al. Anti-calmodulins and Tricyclic Adjuvants in Pain Therapy Block the TRPV1 Channel[J]. Plos One, 2007, 2(6):e545.

Dickerson J B, Morgan M A, Mishra A, et al. The influence of phosphorylation on the activity and structure of the neuronal IQ motif protein, PEP-19[J]. Brain Research, 2006, 1092(1):16-27.

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