Literature DB >> 30883119

Discovery of Bisubstrate Inhibitors for Protein N-Terminal Methyltransferase 1.

Dongxing Chen1, Guangping Dong1, Nicholas Noinaj2, Rong Huang1.   

Abstract

Protein N-terminal methyltransferase 1 (NTMT1) plays an important role in regulating mitosis and DNA repair. Here, we describe the discovery of a potent NTMT1 bisubstrate inhibitor 4 (IC50 = 35 ± 2 nM) that exhibits greater than 100-fold selectivity against a panel of methyltransferases. We also report the first crystal structure of NTMT1 in complex with an inhibitor, which revealed that 4 occupies substrate and cofactor binding sites of NTMT1.

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Year:  2019        PMID： 30883119      PMCID： PMC6760264          DOI： 10.1021/acs.jmedchem.9b00206

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  28 in total

1.  N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis.

Authors:  Ting Chen; Tara L Muratore; Christine E Schaner-Tooley; Jeffrey Shabanowitz; Donald F Hunt; Ian G Macara
Journal:  Nat Cell Biol       Date:  2007-04-15       Impact factor: 28.824

2.  α-N-methylation of damaged DNA-binding protein 2 (DDB2) and its function in nucleotide excision repair.

Authors:  Qian Cai; Lijuan Fu; Zi Wang; Nanqin Gan; Xiaoxia Dai; Yinsheng Wang
Journal:  J Biol Chem       Date:  2014-04-21       Impact factor: 5.157

3.  Occurrence of methylated amino acids as N-termini of proteins from Escherichia coli ribosomes.

Authors:  R Chen; J Brosius; B Wittmann-Liebold
Journal:  J Mol Biol       Date:  1977-04       Impact factor: 5.469

4.  Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).

Authors:  Nicolas Babault; Abdellah Allali-Hassani; Fengling Li; Jie Fan; Alex Yue; Kevin Ju; Feng Liu; Masoud Vedadi; Jing Liu; Jian Jin
Journal:  J Med Chem       Date:  2018-01-31       Impact factor: 7.446

5.  Identification and Functional Characterizations of N-Terminal α-N-Methylation and Phosphorylation of Serine 461 in Human Poly(ADP-ribose) Polymerase 3.

Authors:  Xiaoxia Dai; Stuart L Rulten; Changjun You; Keith W Caldecott; Yinsheng Wang
Journal:  J Proteome Res       Date:  2015-04-27       Impact factor: 4.466

6.  PRMT5 modulates the metabolic response to fasting signals.

Authors:  Wen-Wei Tsai; Sherry Niessen; Naomi Goebel; John R Yates; Ernesto Guccione; Marc Montminy
Journal:  Proc Natl Acad Sci U S A       Date:  2013-05-13       Impact factor: 11.205

7.  Identification of novel α-n-methylation of CENP-B that regulates its binding to the centromeric DNA.

Authors:  Xiaoxia Dai; Koichiro Otake; Changjun You; Qian Cai; Zi Wang; Hiroshi Masumoto; Yinsheng Wang
Journal:  J Proteome Res       Date:  2013-08-26       Impact factor: 4.466

8.  DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1 transcription factors in breast cancer progression.

Authors:  Min-Hyung Cho; Ji-Hye Park; Hee-Joo Choi; Mi-Kyung Park; Hee-Young Won; Yeon-Ji Park; Chang Hoon Lee; Seung-Hyun Oh; Young-Soo Song; Hyun Sung Kim; Young-Ha Oh; Jeong-Yeon Lee; Gu Kong
Journal:  Nat Commun       Date:  2015-07-22       Impact factor: 14.919

9.  α-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere.

Authors:  Kizhakke M Sathyan; Daniele Fachinetti; Daniel R Foltz
Journal:  Nat Commun       Date:  2017-03-07       Impact factor: 14.919

Review 10.  Chemical Biology of Protein N-Terminal Methyltransferases.

Authors:  Rong Huang
Journal:  Chembiochem       Date:  2019-02-13       Impact factor: 3.164
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  13 in total

1.  Optimization of High-Throughput Methyltransferase Assays for the Discovery of Small Molecule Inhibitors.

Authors:  Guangping Dong; Adam Yasgar; Darrell L Peterson; Alexey Zakharov; Daniel Talley; Ken Chih-Chien Cheng; Ajit Jadhav; Anton Simeonov; Rong Huang
Journal:  ACS Comb Sci       Date:  2020-06-27       Impact factor: 3.784

2.  Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogues.

Authors:  Dongxing Chen; Cheng Dong; Guangping Dong; Karthik Srinivasan; Jinrong Min; Nicholas Noinaj; Rong Huang
Journal:  J Med Chem       Date:  2020-07-16       Impact factor: 7.446

3.  Selective Peptidomimetic Inhibitors of NTMT1/2: Rational Design, Synthesis, Characterization, and Crystallographic Studies.

Authors:  Brianna D Mackie; Dongxing Chen; Guangping Dong; Cheng Dong; Haley Parker; Christine E Schaner Tooley; Nicholas Noinaj; Jinrong Min; Rong Huang
Journal:  J Med Chem       Date:  2020-08-05       Impact factor: 7.446

4.  Novel Propargyl-Linked Bisubstrate Analogues as Tight-Binding Inhibitors for Nicotinamide N-Methyltransferase.

Authors:  Dongxing Chen; Linjie Li; Krystal Diaz; Iredia D Iyamu; Ravi Yadav; Nicholas Noinaj; Rong Huang
Journal:  J Med Chem       Date:  2019-12-03       Impact factor: 7.446

5.  Exploring Unconventional SAM Analogues To Build Cell-Potent Bisubstrate Inhibitors for Nicotinamide N-Methyltransferase.

Authors:  Iredia D Iyamu; Jonah Z Vilseck; Ravi Yadav; Nicholas Noinaj; Rong Huang
Journal:  Angew Chem Int Ed Engl       Date:  2022-02-23       Impact factor: 15.336

Review 6.  Mechanisms and inhibitors of nicotinamide N-methyltransferase.

Authors:  Iredia D Iyamu; Rong Huang
Journal:  RSC Med Chem       Date:  2021-05-19

Review 7.  Past, present, and perspectives of protein N-terminal methylation.

Authors:  Krystal Diaz; Ying Meng; Rong Huang
Journal:  Curr Opin Chem Biol       Date:  2021-04-08       Impact factor: 8.972

8.  Structure-based Discovery of Cell-Potent Peptidomimetic Inhibitors for Protein N-Terminal Methyltransferase 1.

Authors:  Dongxing Chen; Guangping Dong; Youchao Deng; Nicholas Noinaj; Rong Huang
Journal:  ACS Med Chem Lett       Date:  2021-03-01       Impact factor: 4.632

Review 9.  Histone N-alpha terminal modifications: genome regulation at the tip of the tail.

Authors:  Christina Demetriadou; Costas Koufaris; Antonis Kirmizis
Journal:  Epigenetics Chromatin       Date:  2020-07-17       Impact factor: 4.954

10.  Chemoproteomic Study Uncovers HemK2/KMT9 As a New Target for NTMT1 Bisubstrate Inhibitors.

Authors:  Dongxing Chen; Ying Meng; Dan Yu; Nicholas Noinaj; Xiaodong Cheng; Rong Huang
Journal:  ACS Chem Biol       Date:  2021-06-30       Impact factor: 4.634
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