title: N-terminal region of the catalytic domain of human N-myristoyltransferase 1 acts as an inhibitory module.
abstract: N-myristoyltransferase (NMT) plays critical roles in the modulation of various signaling molecules, however, the regulation of this enzyme in diverse cellular states remains poorly understood. We provide experimental evidence to show for the first time that for the isoform 1 of human NMT (hNMT1), the regulatory roles extend into the catalytic core. In our present study, we expressed, purified, and characterized a truncation mutant devoid of 28 N-terminal amino acids from the catalytic module (Δ28-hNMT1s) and compared its properties to the full-length catalytic domain of hNMT1. The deletion of the N-terminal peptide had no effect on the enzyme stability. Our findings suggest that the N-terminal region in the catalytic module of hNMT1 functions serves as a regulatory control element. The observations of an ~3 fold increase in enzymatic efficiency following removal of the N-terminal peptide of hNMT1s indicates that N-terminal amino acids acts as an inhibitory segment and negatively regulate the enzyme activity. Our findings that the N-terminal region confers control over activity, taken together with the earlier observations that the N-terminal of hNMT1 is differentially processed in diverse cellular states, suggests that the proteolytic processing of the peptide segment containing the inhibitory region provides a molecular mechanism for physiological up-regulation of myristoyltransferase activity.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Sujeet
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D020134:Catalytic Domain / Q000235:genetics; D006801:Humans; D011499:Protein Processing, Post-Translational; D015854:Up-Regulation
chemical_list: D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase