Modeling the mechanisms of biological GTP hydrolysis.
Enzymes that hydrolyze GTP are currently in the spotlight, due to their molecular switch mechanism that controls many cellular processes. One of the best-known classes of these enzymes are small GTPases such as members of the Ras superfamily, which catalyze the hydrolysis of the γ-phosphate bond in GTP. In addition, the availability of an increasing number of crystal structures of translational GTPases such as EF-Tu and EF-G have made it possible to probe the molecular details of GTP hydrolysis on the ribosome. However, despite a wealth of biochemical, structural and computational data, the way in which GTP hydrolysis is activated and regulated is still a controversial topic and well-designed simulations can play an important role in resolving and rationalizing the experimental data. In this review, we discuss the contributions of computational biology to our understanding of GTP hydrolysis on the ribosome and in small GTPases.
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, SE-751 24 Uppsala, Sweden.
Alexandra T P
AT
Carvalho
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, SE-751 24 Uppsala, Sweden.
Klaudia
K
Szeler
Copenhagen Plant Science Centre (CPSC), Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
Konstantinos
K
Vavitsas
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, SE-751 24 Uppsala, Sweden.
Johan
J
Åqvist
Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, SE-751 24 Uppsala, Sweden. Electronic address: kamerlin@icm.uu.se.
Shina C L
SC
Kamerlin
D019295:Computational Biology; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D008954:Models, Biological; D010444:Peptide Elongation Factor Tu / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D006160:Guanosine Triphosphate; D010444:Peptide Elongation Factor Tu; D018631:ras Proteins
Computational biology; EF-G; EF-Tu; GTP hydrolysis; Ras GTPase