A Single Genomic Copy of an Engineered Methionyl-tRNA Synthetase Enables Robust Incorporation of Azidonorleucine into Recombinant Proteins inE. coli

2009 ◽  
Vol 131 (47) ◽  
pp. 17078-17079 ◽  
Author(s):  
Diya M. Abdeljabbar ◽  
Thomas J. Klein ◽  
Siyan Zhang ◽  
A. James Link
Keyword(s):  
Recombinant Proteins ◽  
Trna Synthetase ◽  
Genomic Copy ◽  
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 Introduction of an Aliphatic Ketone into Recombinant Proteins in a Bacterial Strain that Overexpresses an Editing-Impaired Leucyl-tRNA Synthetase

ChemBioChem ◽  
2009 ◽  
Vol 10 (13) ◽  
pp. 2188-2190 ◽  
Author(s):  
Yi Tang ◽  
Pin Wang ◽  
James A. Van Deventer ◽  
A. James Link ◽  
David A. Tirrell
Keyword(s):  
Recombinant Proteins ◽  
Bacterial Strain ◽  
Trna Synthetase ◽  
Aliphatic Ketone

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.

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