@entity369 kinase is a member of the @entity69907 kinase family that includes @entity908 kinase and likely shares a common reaction mechanism in catalyzing the buffering of cellular @entity855 energy levels. Abstraction of a proton from the substrate @entity2097 by a catalytic base has long been thought to be an early mechanistic step. The structure of @entity369 kinase as a transition state analog complex (Zhou, G., Somasundaram, T., Blanc, E., Parthasarathy, G., Ellington, W. R., and Chapman, M. S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 8449-8454) showed that @entity367 -225 and @entity367 -314 were the only potential catalytic residues contacting the phosphorylated @entity1568 . In the present study, these residues were changed to @entity2574 , @entity7647 , and @entity2596 or Ala in several single and multisite mutant enzymes. These mutations had little impact on the substrate binding constants. The effect upon activity varied with reductions in kcat between 3000-fold and less than 2-fold. The retention of significant activity in some mutants contrasts with published studies of homologues and suggests that acid-base catalysis by these residues may enhance the rate but is not absolutely essential. Crystal structures of mutant enzymes @entity70392 at 1.9 A and @entity70393 at 2.8 A resolution showed that the precise alignment of substrates is subtly distorted. Thus, pre-ordering of substrates might be just as important as acid-base chemistry, electrostatics, or other potential effects in the modest impact of these residues upon catalysis.

The putative catalytic bases have, at most, an accessory role in the mechanism of XXXX kinase.

@entity1568 :: ('MESH:D009584', 'Chemical') :: ['nitrogen'] @entity70392 :: ('p|SUB|E|314|D', 'ProteinMutation') :: ['E314D'] @entity908 :: ('MESH:D003401', 'Chemical') :: ['creatine'] @entity70393 :: ('p|SUB|E|225|Q', 'ProteinMutation') :: ['E225Q'] @entity2097 :: ('MESH:D019791', 'Chemical') :: ['guanidinium'] @entity7647 :: ('CHEBI:32668', 'Chemical') :: ['Gln'] @entity367 :: ('CHEBI:18237', 'Chemical') :: ['Glu'] @entity2596 :: ('CHEBI:16414', 'Chemical') :: ['Val'] @entity369 :: ('CHEBI:29016', 'Chemical') :: ['arginine', 'Arginine'] @entity2574 :: ('CHEBI:22660', 'Chemical') :: ['Asp'] @entity69907 :: ('CHEBI:64618', 'Chemical') :: ['phosphagen'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP']
@entity369 :: (CHEBI:29016,Chemical) :: ['arginine']
