The role of conserved water molecules in the catalytic domain of protein kinases.
Protein kinases are essential signaling molecules with a characteristic bilobal shape that has been studied for over 15 years. Despite the number of crystal structures available, little study has been directed away from the prototypical functional elements of the kinase domain. We have performed a structural alignment of 13 active-conformation kinases and discovered the presence of six water molecules that occur in conserved locations across this group of diverse kinases. Molecular dynamics simulations demonstrated that these waters confer a great deal of stability to their local environment and to a key catalytic residue. Our results highlight the importance of novel elements within the greater kinase family and suggest that conserved water molecules are necessary for efficient kinase function.
Ottawa Hospital Research Institute, Ontario, Canada.
James D R
JD
Knight
Donald
D
Hamelberg
J Andrew
JA
McCammon
Rashmi
R
Kothary
D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D006860:Hydrogen Bonding; D051379:Mice; D008958:Models, Molecular; D011494:Protein Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D051381:Rats; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D014867:Water; D011494:Protein Kinases