title: Glycine in the conserved motif III modulates the thermostability and oxidative stress resistance of peptide deformylase in Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Biotechnology Division, National Institute for Interdisciplinary Science and Technology (NIIST), CSIR, Trivandrum, India.
authors.forename: Sai Shyam
authors.initials: SS
authors.lastname: Narayanan
authors.forename: Pandian
authors.initials: P
authors.lastname: Sokkar
authors.forename: Murugesan
authors.initials: M
authors.lastname: Ramachandran
authors.forename: Kesavan Madhavan
authors.initials: KM
authors.lastname: Nampoothiri
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004795:Enzyme Stability; D005998:Glycine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D000581:Amidohydrolases; C084507:peptide deformylase; D005998:Glycine