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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Richardson, Stacie L. Hanjra, Pahul Peterson, Darrell L. Zhang, Gang Huang, Rong Mao, Yunfei |
| Description | Author Affiliation: Richardson SL ( From the Department of Medicinal Chemistry, the Institute for Structural Biology and Drug Discovery, and.); Mao Y ( From the Department of Medicinal Chemistry, the Institute for Structural Biology and Drug Discovery, and.); Zhang G ( From the Department of Medicinal Chemistry, the Institute for Structural Biology and Drug Discovery, and.); Hanjra P ( From the Department of Medicinal Chemistry, the Institute for Structural Biology and Drug Discovery, and.); Peterson DL ( the Institute for Structural Biology and Drug Discovery, and the Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23219.); Huang R ( From the Department of Medicinal Chemistry, the Institute for Structural Biology and Drug Discovery, and rhuang@vcu.edu.) |
| Abstract | The protein N-terminal methyltransferase 1 (NTMT1) catalyzes the transfer of the methyl group from the S-adenosyl-l-methionine to the protein -amine, resulting in formation of S-adenosyl-l-homocysteine and -N-methylated proteins. NTMT1 is an interesting potential anticancer target because it is overexpressed in gastrointestinal cancers and plays an important role in cell mitosis. To gain insight into the biochemical mechanism of NTMT1, we have characterized the kinetic mechanism of recombinant NTMT1 using a fluorescence assay and mass spectrometry. The results of initial velocity, product, and dead-end inhibition studies indicate that methylation by NTMT1 proceeds via a random sequential Bi Bi mechanism. In addition, our processivity studies demonstrate that NTMT1 proceeds via a distributive mechanism for multiple methylations. Together, our studies provide new knowledge about the kinetic mechanism of NTMT1 and lay the foundation for the development of mechanism-based inhibitors. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 18 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Protein Methyltransferases Metabolism Amino Acid Sequence Biocatalysis Enzyme Inhibitors Pharmacology Kinetics Methylation Antagonists & Inhibitors Chemistry Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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