Catalytic mechanism of the tryptophan activation reaction revealed by crystal structures of human tryptophanyl-tRNA synthetase in different enzymatic states.

ABSTRACT: Human tryptophanyl-tRNA synthetase (hTrpRS) differs from its bacterial counterpart at several key positions of the catalytic active site and has an extra N-terminal domain, implying possibly a different catalytic mechanism. We report here the crystal structures of hTrpRS in complexes with Trp, tryptophanamide and ATP and tryptophanyl-AMP, respectively, which represent three different enzymatic states of the Trp activation reaction. Analyses of these structures reveal the molecular basis of the mechanisms of the substrate recognition and the activation reaction. The dimeric hTrpRS is structurally and functionally asymmetric with half-of-the-sites reactivity. Recognition of Trp is by an induced-fit mechanism involving conformational change of the AIDQ motif that creates a perfect pocket for

SUBMITTER: Shen N 

PROVIDER: S-EPMC2275098 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature