4asu
F1-ATPase in which all three catalytic sites contain bound nucleotide, with magnesium ion released in the Empty site
Structural highlights
FunctionATPA_BOVIN Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity). Publication Abstract from PubMedThe molecular description of the mechanism of F(1)-ATPase is based mainly on high-resolution structures of the enzyme from mitochondria, coupled with direct observations of rotation in bacterial enzymes. During hydrolysis of ATP, the rotor turns counterclockwise (as viewed from the membrane domain of the intact enzyme) in 120 degrees steps. Because the rotor is asymmetric, at any moment the three catalytic sites are at different points in the catalytic cycle. In a "ground-state" structure of the bovine enzyme, one site (beta(E)) is devoid of nucleotide and represents a state that has released the products of ATP hydrolysis. A second site (beta(TP)) has bound the substrate, magnesium. ATP, in a precatalytic state, and in the third site (beta(DP)), the substrate is about to undergo hydrolysis. Three successive 120 degrees turns of the rotor interconvert the sites through these three states, hydrolyzing three ATP molecules, releasing the products and leaving the enzyme with two bound nucleotides. A transition-state analog structure, F(1)-TS, displays intermediate states between those observed in the ground state. For example, in the beta(DP)-site of F(1)-TS, the terminal phosphate of an ATP molecule is undergoing in-line nucleophilic attack by a water molecule. As described here, we have captured another intermediate in the catalytic cycle, which helps to define the order of substrate release. In this structure, the beta(E)-site is occupied by the product ADP, but without a magnesium ion or phosphate, providing evidence that the nucleotide is the last of the products of ATP hydrolysis to be released. Structural evidence of a new catalytic intermediate in the pathway of ATP hydrolysis by F1-ATPase from bovine heart mitochondria.,Rees DM, Montgomery MG, Leslie AG, Walker JE Proc Natl Acad Sci U S A. 2012 Jun 25. PMID:22733764[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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