Is myosin a "back door" enzyme?
ATP has been modeled into the active site of chicken skeletal myosin subfragment-1 using the adenylate kinase.Ap5A structure as a starting reference. The resulting docked ATP.S1 structure is justified in that it rationalizes the photolabeling data from several ATP analogs. The gamma-phosphate of ATP sits at the bottom of the active site pocket and is partially visible via a view along the prominent 50-kDa cleft of S1 but not when viewed from above the active site. It is postulated that actin binding promotes the movement of the P-loop and Arg-245 to allow Pi from ATP to leave via a "back-door" in the 50-kDa fragment while ADP is still bound at the active site. Such a mechanism can explain a number of experimental observations, including the kinetics of ATP hydrolysis, the nucleotide dependence of Pi exchange into ATP, and the formation of stable myosin.ADP.vanadate complexes in muscle fibers.
Yount
R G
RG
Department of Biochemistry and Biophysics, Washington State University, Pullman 99164, USA.
Lawson
D
D
Rayment
I
I
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D002645:Chickens; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D009119:Muscle Contraction / Q000502:physiology; D009132:Muscles / Q000201:enzymology / Q000378:metabolism; D015879:Myosin Subfragments / Q000737:chemistry* / Q000378:metabolism*
D015879:Myosin Subfragments; D000255:Adenosine Triphosphate