scholarly journals Stabilization of Cyclin-Dependent Kinase 4 by Methionyl-tRNA Synthetase in p16INK4a-Negative Cancer

2018 ◽  
Vol 1 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Nam Hoon Kwon ◽  
Jin Young Lee ◽  
Ye-lim Ryu ◽  
Chanhee Kim ◽  
Jiwon Kong ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Cyclin Dependent Kinase ◽  
Methionyl Trna Synthetase

scholarly journals A MUTANT OF YEAST WITH A DEFECTIVE METHIONYL-tRNA SYNTHETASE

Genetics ◽  
1969 ◽  
Vol 61 (3) ◽  
pp. 557-566
Author(s):  
Calvin S McLaughlin ◽  
Leland H Hartwell
Keyword(s):  
Trna Synthetase ◽  
Methionyl Trna Synthetase

scholarly journals Misacylation of specific nonmethionyl tRNAs by a bacterial methionyl-tRNA synthetase

2011 ◽  
Vol 108 (17) ◽  
pp. 6933-6938 ◽  
Author(s):  
T. E. Jones ◽  
R. W. Alexander ◽  
T. Pan
Keyword(s):  
Trna Synthetase ◽  
Methionyl Trna Synthetase

scholarly journals Structure-based drug design against Trypanosoma brucei methionyl-tRNA synthetase

2014 ◽  
Vol 70 (a1) ◽  
pp. C708-C708
Author(s):  
Cho Yeow Koh ◽  
Jasmine Nguyen ◽  
Sayaka Shibata ◽  
Zhongsheng Zhang ◽  
Ranae Ranade ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Trypanosoma Brucei ◽  
High Throughput ◽  
High Throughput Screening ◽  
Protozoan Parasite ◽  
Trna Synthetase ◽  
Structure Based Drug Design ◽  
Chemical Structures ◽  
Ic50 Values ◽  
Methionyl Trna Synthetase

Infection by the protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, commonly known as sleeping sickness. The disease is fatal without treatment; yet, current therapeutic options for the disease are inadequate due to toxicity, difficulty in administration and emerging resistance. Therefore, methionyl-tRNA synthetase of T. brucei (TbMetRS) is targeted for the development of new antitrypanosomal drugs. We have recently completed a high-throughput screening campaign against TbMetRS using a 364,131 compounds library in The Scripps Research Institute Molecular Screening Center. Here we outline our strategy to integrate the power of crystal structures with high-throughput screening in a drug discovery project. We applied the rapid crystal soaking procedure to obtain structures of TbMetRS in complex with inhibitors reported earlier[1] to approximately 70 high-throughput screening hits. This resulted in more than 20 crystal structures of TbMetRS·hit complexes. These hits cover a large diversity of chemical structures with IC50 values between 200 nM and 10 µM. Based on the solved structures and existing knowledge drawn from other in-house inhibitors, the IC50 value of the most promising hit has been improved. Further development of the compounds into potent TbMetRS inhibitors with desirable pharmacokinetic properties is on-going and will continue to benefit from information derived from crystal structures.

Sign in / Sign up

Export Citation Format

Share Document