Comparative structural dynamics of Tyrosyl-tRNA synthetase complexed with different substrates explored by molecular dynamics

Several molecular dynamics simulations of S. aureus Tyrosyl-tRNA synthetase (TyrRS) in its free form and complexed with Tyr, ATP, tyrosyl adenylate and inhibitor respectively have been carried out to investigate the ligand-linked conformational stability changes associated with its catalytic cycle. The results show that unliganded S. aureus TyrRS samples a more relaxed conformational space than substrate-bound TyrRS. There are three high flexibility regions encompassing residues 114-118, 128-133, and 226-238 respectively. The region which includes the KMSKS motif (KFGKS in S. aureus TyrRS) shows the highest difference in fluctuations. Hydrogen bond network formed by Tyr, ATP, tyrosyl adenylate and inhibitor with S. aureus TyrRS is discussed. Our simulations suggest the induced-fit conformational changes of the KMSKS loop as follows: the KMSKS loop of substrate-free S. aureus TyrRS adopts an open conformation. The tyrosine binds in the pocket with the KMSKS loop balancing between semi-open and open forms. The ATP binding induces the KMSKS loop to the open form. After the Tyr-AMP is formed, the first two residues of KMSKS loop twists in an anticlockwise direction and drives the loop in a conformation similar to the closed one, while those of the last three GKS residues adopt a conformation between semi-open and open conformation. This conformational change may probably be involved in the initial tRNA binding.

Jaar van publicatie:2008

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:1

CSS-citation score:1

Authors from:Higher Education

Toegankelijkheid:Closed