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In Silico Characterization of Atypical Kinase PFD0975w from Plasmodium Kinome: A Suitable Target For Drug Discovery
Author(s) -
Trivedi Vishal,
Nag Swagata
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01321.x
Subject(s) - kinome , peptide , in silico , plasmodium falciparum , computational biology , biochemistry , biology , binding site , drug discovery , protein kinase domain , ribosome biogenesis , kinase , biogenesis , cyclic nucleotide binding domain , peptide sequence , chemistry , microbiology and biotechnology , ribosome , rna , malaria , mutant , immunology , gene
RIO‐2 kinase is known to regulate ribosome biogenesis and other cell cycle events. The 3D model of ATP bound and an unbound form of PFD0975w was generated using AfRIO‐2 crystal structure 1TQI, 1ZAO as template employing M odeller 9v7 program. Structural characterization identified N‐terminal winged helix domain (1–84), C‐terminal kinase domain (148–275), and presence of other critical residues known for ATP binding and kinase activity. Using Q‐site and pocket finder, a number of well‐defined substrate (peptide) binding regions were identified in the catalytic core of the protein. The peptide binding regions were further validated by molecular modeling a non‐specific polyalanine peptide and a sequence‐specific peptide2 into these sites to generate a stable PFD0975w/peptide complexes. Peptide fits well into identified pocket on PFD0975w and makes extensive interaction with the protein residues. These newly identified peptide binding sites potentially give opportunity to design a specific inhibitor against PFD0975w. There are subtle but significant differences between Plasmodium falciparum and human RIO‐2 to exploit PFD0975w for drug development. In conclusion, our finding will let us to design effective chemotherapy against malaria parasite exploiting PFD0975w as a drug target.