Open AccessGlycine in the conserved motif III modulates the thermostability and oxidative stress resistance of peptide deformylase in Mycobacterium tuberculosis
Author(s) -
Narayanan Sai Shyam,
Sokkar Pandian,
Ramachandran Murugesan,
Nampoothiri Kesavan Madhavan
Publication year - 2011
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2011.02289.x
Subject(s) - thermostability , biochemistry , mycobacterium tuberculosis , peptide , mutant , enzyme , chemistry , mycobacterium , biology , bacteria , tuberculosis , gene , genetics , medicine , pathology
Peptide deformylase (PDF) catalyses the removal of the N ‐formyl group from the nascent polypeptide during protein maturation. The PDF of Mycobacterium tuberculosis H37Rv (MtbPDF), overexpressed and purified from Escherichia coli , was characterized as an iron‐containing enzyme with stability towards H 2 O 2 and moderate thermostability. Substitution of two conserved residues (G49 and L107) from MtbPDF with the corresponding residues found in human PDF affected its deformylase activity. Among characterized PDFs, glycine (G151) in motif III instead of conserved aspartate is characteristic of M. tuberculosis . Although the G151D mutation in MtbPDF increased its deformylase activity and thermostability, it also affected enzyme stability towards H 2 O 2 . Molecular dynamics and docking results confirmed improved substrate binding and catalysis for the G151D mutant and the study provides another possible molecular basis for the stability of MtbPDF against oxidizing agents.