Biochemical characterization of bovine brain myristoyl-CoA:protein N-myristoyltransferase type 2.
Protein N-myristoylation is a lipidic modification which refers to the covalent attachment of myristate, a 14-carbon saturated fatty acid, to the N-terminal glycine residue of a number of mammalian, viral, and fungal proteins. In this paper, we have cloned the gene coding for myristoyl-CoA:protein N-myristoyltransferase (NMT) from Bos tarus brain. The open reading frame codes for a 410-amino-acid protein and overexpressed in Escherichia coli. Kinetic studies suggested that bovine brain NMT2 and human NMT1 show significant differences in their peptide substrate specificities. The metal ion Ca(2+) had stimulatory effects on NMT2 activity while Mn(2+) and Zn(2+) inhibited the enzyme activity. In addition, NMT2 activity was inhibited by various organic solvents and other detergents while NMT1 had a stimulatory effect. Biochemical characterization suggested that both forms of NMT have unique characteristics. Further analysis towards functional role NMT2 will lead the development of therapeutic target for the progression of various diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases.
Selvakumar
Ponniah
P
Department of Pathology and Laboratory Medicine, College of Medicine and Health Research Division, Saskatchewan Cancer Agency, University of Saskatchewan, SK, Canada.
Lakshmikuttyamma
Ashakumary
A
Sharma
Rajendra K
RK
D000217:Acyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000737:chemistry; D002417:Cattle; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry; D008345:Manganese / Q000737:chemistry; D008969:Molecular Sequence Data; D010802:Phylogeny; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
D011994:Recombinant Proteins; D012997:Solvents; D012967:Sodium Dodecyl Sulfate; D008345:Manganese; D000217:Acyltransferases; D008274:Magnesium; D015032:Zinc; D002118:Calcium