Premium
Why does mutation of G ln61 in Ras by the nitro analog NG ln maintain activity of R as‐ GAP in hydrolysis of guanosine triphosphate?
Author(s) -
Khrenova Maria G.,
Grigorenko Bella L.,
Mironov Vladimir A.,
Nemukhin Alexander V.
Publication year - 2015
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24927
Subject(s) - guanosine , chemistry , gtp' , enzyme , guanosine triphosphate , biochemistry , stereochemistry , hydrolysis , substrate (aquarium) , g protein , nitro , signal transduction , biology , organic chemistry , ecology , alkyl
Interpretation of the experiments showing that the Ras‐GAP protein complex maintains activity in guanosine triphosphate (GTP) hydrolysis upon replacement of Glu61 in Ras with its unnatural nitro analog, NGln, is an important issue for understanding details of chemical transformations at the enzyme active site. By using molecular modeling we demonstrate that both glutamine and its nitro analog in the aci ‐nitro form participate in the reaction of GTP hydrolysis at the stages of proton transfer and formation of inorganic phosphate. The computed structures and the energy profiles for the complete pathway from the enzyme‐substrate to enzyme‐product complexes for the wild‐type and mutated Ras suggest that the reaction mechanism is not affected by this mutation. Proteins 2015; 83:2091–2099. © 2015 Wiley Periodicals, Inc.