6R1O

Crystal structure of E. coli seryl-tRNA synthetase complexed to a seryl sulfamoyl adenosine derivative

Summary for 6R1O

• Entry DOI: 10.2210/pdb6r1o/pdb
• Descriptor: Serine--tRNA ligase, [(2~{R},3~{S},4~{R},5~{R})-5-(6-azanyl-2-pyridin-3-yl-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl ~{N}-[(2~{S})-2-azanyl-3-oxidanyl-propanoyl]sulfamate, CHLORIDE ION, ... (8 entities in total)
• Functional Keywords: aminoacyl-trna synthetase, class ii, protein synthesis, inhibitor, ligase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 51893.45

Authors

Salimraj, R.,Cain, R.,Roper, D.I. (deposition date: 2019-03-14, release date: 2020-01-22, Last modification date: 2024-01-24)

Primary citation

Cain, R.,Salimraj, R.,Punekar, A.S.,Bellini, D.,Fishwick, C.W.G.,Czaplewski, L.,Scott, D.J.,Harris, G.,Dowson, C.G.,Lloyd, A.J.,Roper, D.I.
Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.
J.Med.Chem., 62:9703-9717, 2019

PubMed Abstract: Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high-resolution X-ray crystal structures of the and seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than 2 orders of magnitude compared to their human homologue, demonstrating a route to the selective chemical inhibition of these bacterial targets.

PubMed: 31626547
DOI: 10.1021/acs.jmedchem.9b01131

Experimental method

X-RAY DIFFRACTION (2.6 Å)