Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The original aim of the review has been to probe into the validity of the paradigm on the high energy-carrier function of ATP. It seemed to be called into question on the basis of findings with H(+)-transporting ATP synthase suggesting the formation of ATP from ADP and Pi without energy input. Thus, ATP appeared as a low-energy compound. Starting from the current, rich knowledge of the molecular structure and the inviting thinking on the mechanism of H(+)-transporting ATP synthase, we have endeavoured to freshly interpret and integrate the pertinent observations in the light of the comprehensively derived model of the molecular mechanism of energy interconversion by Na+/K(+)-transporting ATPase. In this way, we have uncovered the common mechanistic elements of the two energy-interconverting enzymes. The emerging purpose of the present paper has been the 'synthesis' of a self-contained concept of the molecular mechanism of the interconversion of electrochemical and chemical Gibbs energies by H(+)-transporting ATP synthase. The outcome is reflected in the following tentative evaluations. 1. In ATP hydrolysis, the great Gibbs energy change which is observed in solution, is largely conserved by the F1 sector of ATP synthase as mechanical Gibbs energy in the enzyme's protein fabric, so that it can be utilized in the resynthesis of ATP from enzyme-bound ADP and Pi. The plainly measured low Gibbs energy change results from large compensating enthalpy and entropy changes that reflect the underlying changes in protein conformation. 2. In stoichiometric ATP synthesis by F1 sector from ADP and Pi bound to the catalytic centre, their intrinsic binding energy brings about a loss of peptide chain entropy that makes possible an entropy-driven ATP formation. 3. The driving force for ATP synthesis cannot be the high Gibbs energy change on binding of product ATP; the tight ATP-enzyme complex rather is a low Gibbs energy intermediate from which escape is difficult. 4. The catalytic centre exists either in an open state unable to firmly bind the substrate-product couple, or in a closed state protecting formed ATP from facile hydrolysis by ambient water. 5. The cleft closure, induced by binding of Pi and ADP or ATP, does not necessarily need external energy supply, because the cleft closure proceeds from rigid domain rotations which can occur rather spontaneously. In further analogy to adenylate kinase, the driving force of this domain movement presumably comes from the electrostatic interactions between phosphate moieties and arginine side chains in the catalytic centre.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Synthesis of a self-contained concept of the molecular mechanism of energy interconversion by H(+)-transporting ATP synthase. 805 42

Subunit c of the F1F0 type, H(+)-transporting ATP synthase contains an essential Asp that is thought to function in H+ transport. Subunit c folds as a helical hairpin of two transmembrane helices with the essential Asp centered at residue 61 in transmembrane helix-2. Miller et al. (Miller, M. J., Olderburg, M., and Fillingame, R. H. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 4900-4904) have described a functional subunit c variant in which the essential Asp was moved from helix-2 to residue 24 on helix-1 with replacement of Asp61 by Gly. The function of the A24D/D61G subunit c variant is not optimal. In this study, 11 position 61 variants of an A24D subunit c were generated by site-directed mutagenesis in order to test the importance of the position 61 residue. Three functional combinations were found with activities in the order:A24D/D61N > A24D/D61G > or = A24D/D61S. Other substitutions at position 61, including Ala and Cys, did not support function in the A24D protein. Although the A24D/D61N variant showed the highest rates of ATPase-coupled H+ transport, its F0 was inactive in passive H+ transport when F1 was stripped from the membrane. On the other hand, passive H+ transport by A24D/D61G and A24D/D61S stripped membranes approached that of wild type. The defect in function in these two mutants must be ascribed to events related to coupling ATPase and H+ transport. An A24D subunit c (with Asp at both position 24 and 61) was also generated. Its function proved to be pH-dependent. Activity approaching that of wild type was observed at pH 7.0, but function was almost completely lost at pH 7.8. The pH-dependent loss of ATP synthase function led to a slowing of growth on succinate as carbon source on raising the pH from 7.0 to 7.8. In the A24D mutant, with a second Asp at position 61, we postulate that 1 Asp must be protonated before the other can function in H+ transport.
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PMID:Essential aspartate in subunit c of F1F0 ATP synthase. Effect of position 61 substitutions in helix-2 on function of Asp24 in helix-1. 810 29

H(+)-transporting ATP synthase is a multi-subunit enzyme involved in the production of ATP, which is an essential molecule for living organisms as a source of energy. Archaeal A-type ATPase (A-ATPase) is thought to act as a functional ATP synthase in archaea and is thought to have chimeric properties of F-ATPase and V-ATPase. Previous structural studies of F-ATPase indicated that the major nucleotide-binding subunits alpha and beta consist of three domains. The catalytic nucleotide-binding subunit A of V/A-ATPase contains an insertion of about 90 residues which is absent from the F(1)-ATPase beta subunit. Here, the first X-ray structure of the catalytic nucleotide-binding subunit A of an A(1)-ATPase is described, determined at 2.55 A resolution. A(1)-ATPase subunit A from Pyrococcus horikoshii consists of four domains. A novel domain, including part of the insertion, corresponds to the 'knob-like structure' observed in electron microscopy of A(1)-ATPase. Based on the structure, it is highly likely that this inserted domain is related to the peripheral stalk common to the A- and V-ATPases. The arrangement of this inserted domain suggests that this region plays an important role in A-ATPase as well as in V-ATPase.
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PMID:Structure of the catalytic nucleotide-binding subunit A of A-type ATP synthase from Pyrococcus horikoshii reveals a novel domain related to the peripheral stalk. 1662 40