ATPases catalytic mechanism

Weber, J. Senior, A.E. (1997) Catalytic mechanism of Fi-ATPase. Biochim. Biophys. Acta 1319, 19-58. 

The nucleotide occupancy of the catalytic sites observed in the first crystal structure was exactly what Paul Boyer had predicted earlier in his binding-change model of cooperative catalysis (Boyer, 1993). Consequently, this first high-resolution structure of the Fj-ATPase immediately initiated a number of studies that ultimately led to the elucidation of the F -. TPase s rotational mechanism of cooperative catalysis. At the time, the F - ATPase structure represented the largest asymmetric structure solved to atomic resolution by x-ray crystallography, and this accomplishment, together with the visionary prediction of rotary catalysis, was subsequently awarded the 1997 Nobel prize in chemistry (to John Walker for the structure and Paul Boyer for the catalytic mechanism). However, whether the first (and many subsequent) structure (s) represented physiologically... 

Weber, J. and Senior, A. E. (1997) Catalytic mechanism ofFl-ATPase, Biochim. Biophys. Acta 1319, 19-58. Wei, C-C., Wang, Z-Q., Wang., Q., Meade, A. L., Hemann, C., Hille, R., and Stuehr, D.J. (2001) Rapid kinetic stadies link tetrahydrobiopterin radical formation to heme-dioxy redyction and arginine hydroxylation in inducible nitric-oxide synthase, J. Biol Chem. 276, 315-319. 

Hundreds of mutant P-type ATPases have been generated in an effort to understand the catalytic mechanism and regulation of these enzymes. Functional analysis of these mutants has established the roles of particular domains and amino acid residues in the overall catalysis of cation translocation and allowed structure prediction (MacLennan etal., 1997) (Figs. 1 and 2). Recently the 3-D or crystal structures of Ca +, H+, and Na+/K+ P-type ATPases have been resolved, and they confirmed findings... 

Active transport is often carried out at the expense of ATP hydrolysis. P-type ATPases pump ions against a concentration gradient and become transiently phosphorylated on an aspartic acid residue in the process of transport. P-type ATPases, which include the sarcoplasmic reticulum Ca2+ ATPase and the Na+-K+ ATPase, are integral membrane proteins with conserved structures and catalytic mechanisms. 

V. Kabaleeswaran, N. Puri, J.E. Walker, A.G.W. Leslie, D.M. Mueller, Novel features of the rotary catalytic mechanism revealed in the structure of yeast F i ATPase. EMBO J. 25, 5433-5442, (2006)... 

Walmsley AR, T Zhou, Ml Boirges-Walmsley, BP Rosen (1999) The ATPase mechanism of ArsA, the catalytic subunit of the arsenite pump. J Biol Chem 274 16153-16161. 

Unisite catalysis is a non-physiological mode of catalysis in which a very small fraction of the enzyme population contains bound nucleotide in all three catalytic sites. According to the torsional mechanism, only this fraction will contribute to the measured ATPase activity. Based on the site occupancies predicted by the torsional mechanism during ATP hydrolysis (two catalytic sites contain bound MgATP, while one contains bound MgADP -i- PJ, the fraction f in Eq. (9) is predicted to be 0.33, which is in perfect agreement with experiment [48]. 

Menz, R. I., Walker, J. E., and Leslie, A. G. (2001). Structure of bovine mitochondrial F(l)-ATPase with nucleotide bound to all three catalytic sites Implications for the mechanism of rotary catalysis. Cell 106, 331-341. 

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