Large-scale movement of functional domains facilitates aminoacylation by human mitochondrial phenylalanyl-tRNA synthetase

FEBS Lett. 2009 Oct 6;583(19):3204-8. doi: 10.1016/j.febslet.2009.09.008. Epub 2009 Sep 6.


Structural studies suggest rearrangement of the RNA-binding and catalytic domains of human mitochondrial PheRS (mtPheRS) is required for aminoacylation. Crosslinking the catalytic and RNA-binding domains resulted in a "closed" form of mtPheRS that still catalyzed ATP-dependent Phe activation, but was no longer able to transfer Phe to tRNA and complete the aminoacylation reaction. SAXS experiments indicated the presence of both the closed and open forms of mtPheRS in solution. Together, these results indicate that conformational flexibility of the two functional modules in mtPheRS is essential for its phenylalanylation activity. This is consistent with the evolution of the aminoacyl-tRNA synthetases as modular enzymes consisting of separate domains that display independent activities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalysis
  • Crystallography, X-Ray
  • Evolution, Molecular
  • Humans
  • Mitochondria / enzymology*
  • Models, Chemical
  • Phenylalanine / metabolism*
  • Phenylalanine-tRNA Ligase / chemistry
  • Phenylalanine-tRNA Ligase / metabolism*
  • Protein Structure, Tertiary
  • RNA, Transfer / metabolism*
  • Scattering, Small Angle
  • Transfer RNA Aminoacylation*


  • Phenylalanine
  • RNA, Transfer
  • Phenylalanine-tRNA Ligase