A hypothesis about myosin catalysis.
When ATP binds to the active site of myosin heads, Switch II undergoes a large conformational change and the cleft surrounding the bound gamma-phosphate closes. In the closed state, Glu470 in Switch II comes together with Arg247 in Switch I to form a salt-bridge. Here, the functional significance of the two bridging residues was tested by using site-directed mutagenesis. We conclude from such tests that (a) the attractive force between Arg247 and the gamma-phosphate of ATP moves the cleft to close, and (b) during hydrolysis, Glu470 is intimately involved in positioning the lytic water for the attack on the gamma-phosphorus. We also speculate on how the salt-bridge between Arg247 and Glu470 is related to hydrolysis.
Onishi
Hirofumi
H
Department of Structural Analysis, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565.
Ohki
Takashi
T
Mozhizuki
Naoki
N
Morales
Manuel F
MF
D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D004023:Dictyostelium; D018698:Glutamic Acid / Q000737:chemistry; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009218:Myosins / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012492:Salts / Q000494:pharmacology
D000199:Actins; D010710:Phosphates; D012492:Salts; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D001120:Arginine; D000251:Adenosine Triphosphatases; D009218:Myosins