Independent saturation of three TrpRS subsites generates a partially assembled state similar to those observed in molecular simulations

Link to Pubmed [PMID] – 19174517

Link to HAL – Click here

Link to DOI – 10.1073/pnas.0812752106

Proc. Natl. Acad. Sci. U.S.A. 2009 Feb;106(6):1790-5

Two new crystal structures of Bacillus stearothermophilus tryptophanyl-tRNA synthetase (TrpRS) afford evidence that a closed interdomain hinge angle requires a covalent bond between AMP and an occupant of either pyrophosphate or tryptophan subsite. They also are within experimental error of a cluster of structures observed in a nonequilibrium molecular dynamics simulation showing partial active-site assembly. Further, the highest energy structure in a minimum action pathway computed by using elastic network models for Open and Pretransition state (PreTS) conformations for the fully liganded TrpRS monomer is intermediate between that simulated structure and a partially disassembled structure from a nonequilibrium molecular dynamics trajectory for the unliganded PreTS. These mutual consistencies provide unexpected validation of inferences drawn from molecular simulations.