bisubstrate analogs
Recently Published Documents


TOTAL DOCUMENTS

13
(FIVE YEARS 0)

H-INDEX

5
(FIVE YEARS 0)

2020 ◽  
Author(s):  
Dongxing Chen ◽  
Cheng Dong ◽  
Guangping Dong ◽  
Karthik Srinivasan ◽  
Jinrong Min ◽  
...  

AbstractThe interactions of a series of bisubstrate analogs with protein N-terminal methyltransferase 1 (NTMT1) were examined to probe the molecular properties of the NTMT1 active site through biochemical characterization and structural studies. Our results indicate that a 2-C to 4-C atom linker enables its respective bisubstrate analog to occupy both substrate and cofactor binding sites of NTMT1, but the bisubstrate analog with a 5-C atom linker only interacts with the substrate binding site and functions as a substrate. Furthermore, the 4-C atom linker is the optimal and produces the most potent inhibitor (Ki, app = 130 ± 40 pM) for NTMT1 to date, displaying over 100,000-fold selectivity over other methyltransferases and 3,000-fold even to its homolog NTMT2. This study reveals the molecular basis for the plasticity of the NTMT1 active site. Additionally, our study outlines a general guidance on the development of bisubstrate inhibitors for any methyltransferases.


RSC Advances ◽  
2016 ◽  
Vol 6 (8) ◽  
pp. 6768-6771 ◽  
Author(s):  
Gang Zhang ◽  
Rong Huang

We report the first chemical synthesis of SAM–peptide conjugates through alkyl linkers to prepare bisubstrate analogs for protein methyltransferases.


1995 ◽  
Vol 5 (8) ◽  
pp. 815-820 ◽  
Author(s):  
Marie-Ange Badet-Denisot ◽  
Caroline Leriche ◽  
Frédéric Massière ◽  
Bernard Badet

1994 ◽  
Vol 5 (5) ◽  
pp. 443-451 ◽  
Author(s):  
Bradford W. Gibson ◽  
Denes Medzihradszky ◽  
Wade M. Hines ◽  
Seppo Auriola ◽  
George L. Kenyon

Sign in / Sign up

Export Citation Format

Share Document