Stabilization of the ADP/metaphosphate intermediate during ATP hydrolysis in pre-power stroke myosin: quantitative anatomy of an enzyme.

ABSTRACT: It has been proposed recently that ATP hydrolysis in ATPase enzymes proceeds via an initial intermediate in which the dissociated γ-phosphate of ATP is bound in the protein as a metaphosphate (PγO3(-)). A combined quantum/classical analysis of this dissociated nucleotide state inside myosin provides a quantitative understanding of how the enzyme stabilizes this unusual metaphosphate. Indeed, in vacuum, the energy of the ADP(3-) · PγO3(-) · Mg(2+) complex is much higher than that of the undissociated ATP(4-). The protein brings it to a surprisingly low value. Energy decomposition reveals how much each interaction in the protein stabilizes the metaphosphate state; backbone peptides of the P-loop contribute 50% of the stabilization energy, and the side chain of Lys-185(+) contributes 25%. Thi

SUBMITTER: Kiani FA 

PROVIDER: S-EPMC3853302 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature