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Novel insights into the regulation of malarial calcium‐dependent protein kinase 1
Author(s) -
Ahmed Anwar,
Gaadhe Kavita,
Sharma Guru Prasad,
Kumar Narendra,
Neculai Mirela,
Hui Raymond,
Mohanty Debasisa,
Sharma Pushkar
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-203877
Subject(s) - plasmodium falciparum , effector , kinase , biology , protein kinase a , microbiology and biotechnology , toxoplasma gondii , plasmodium (life cycle) , malaria , parasite hosting , genetics , immunology , antibody , computer science , world wide web
Calcium‐dependent protein kinases (CDPKs) are major effectors of calcium signaling in apicomplexan parasites like Toxoplasma and Plasmodium and control important processes of the parasite life cycle. Despite recently reported crystal structures of Toxoplasma gondii ( Tg )CDPKs, several important questions about their regulation remain unanswered. Plasmodium falciparum (Pf)CDPK1 has emerged as a key player in the life cycle of the malaria parasite, as it may be involved in the invasion of the host cells. Molecular modeling and site‐directed mutagenesis studies on Pf CDPK1 suggested that several residues in the regulatory domain play a dual role, as they seem to contribute to the stabilization of both the active and inactive kinase. Mass spectrometry revealed that Pf CDPK1 was autophosphorylated at several sites; some of these were placed at strategic locations and therefore were found to be critical for kinase activation. The N‐terminal extension of Pf CDPK1 was found to be important for Pf CDPK1 activation. Unexpectedly, an ATP binding site in the NTE of Pf CDPK1 was identified. Our studies highlight several novel features of Pf CDPK1 regulation, which may be shared by other members of the CDPK family. These findings may also aid design of inhibitors against these important targets, which are absent from the host.—Ahmed, A., Gaadhe, K., Sharma, G. P., Kumar, N., Neculai, M., Hui, R., Mohanty, D., Sharma, P. Novel insights into the regulation of malarial calcium‐dependent protein kinase 1. FASEB J. 26, 3212–3221 (2012). www.fasebj.org