Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The only known cellular action of AlF4- is to stimulate the G-proteins. The aim of the present work is to demonstrate that AlF4- also inhibits 'P'-type cation-transport ATPases. NaF plus AlCl3 completely and reversibly inhibits the activity of the purified (Na+ + K+)-ATPase (Na+- and K+-activated ATPase) and of the purified plasmalemmal (Ca2+ + Mg2+)-ATPase (Ca2+-stimulated and Mg2+-dependent ATPase). It partially inhibits the activity of the sarcoplasmic-reticulum (Ca2+ + Mg2+)-ATPase, whereas it does not affect the mitochondrial H+-transporting ATPase. The inhibitory substances are neither F- nor Al3+ but rather fluoroaluminate complexes. Because AlF4- still inhibits the ATPase in the presence of guanosine 5'-[beta-thio]diphosphate, and because guanosine 5'-[beta gamma-imido]triphosphate does not inhibit the ATPase, it is unlikely that the inhibition could be due to the activation of an unknown G-protein. The time course of inhibition and the concentrations of NaF and AlCl3 required for this inhibition differ for the different ATPases. AlF4- inhibits the (Na+ + K+)-ATPase and the plasmalemmal (Ca2+ + Mg2+)-ATPase noncompetitively with respect to ATP and to their respective cationic substrates, Na+ and Ca2+. AlF4- probably binds to the phosphate-binding site of the ATPase, as the Ki for inhibition of the (Na+ + K+)-ATPase and of the plasmalemmal (Ca2+ + Mg2+)-ATPase is shifted in the presence of respectively 5 and 50 mM-Pi to higher concentrations of NaF. Moreover, AlF4- inhibits the K+-activated p-nitrophenylphosphatase of the (Na+ + K+)-ATPase competitively with respect to p-nitrophenyl phosphate. This AlF4- -induced inhibition of 'P'-type cation-transport ATPases warns us against explaining all the effects of AlF4- on intact cells by an activation of G-proteins.
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PMID:AlF4- reversibly inhibits 'P'-type cation-transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase. 284 38

In the presence of ADP and fluorometals, the ATPase activity of the catalytic sector, F1, of beef heart mitochondrial ATPase is strongly inhibited; this inhibition is dependent on the entrapment of ADP-fluoroaluminate complexes into the nucleotide binding sites of F1 [Lunardi, J., Dupuis, A., Garin, J., Issartel, J. P., Michel, L., Chabre, M., & Vignais, P. V. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8958-8962]. We described here the effect of fluoroaluminate on the binding of 2-azido[3H]ADP and 8-azido[3H]ADP to beef heart mitochondrial F1 in the absence and presence of light. When the incubation medium was supplemented with NaF and AlCl3, and maintained in the dark, both 2-azido[3H]ADP and 8-azido[3H]ADP were able to elicit inhibition of F1-ATPase activity, exactly like ADP did. Upon photoirradiation, 2-azido[3H]ADP and 8-azido[3H]ADP bound covalently to F1. Labeling was restricted to the beta subunit of F1, and the same tyrosine residue, beta-Tyr-345, was labeled by either of the photoprobes. This is in contrast with the previous findings that in the absence of fluoroaluminate both the alpha and beta subunits of F1 were photolabeled by 8-azido[3H]ADP, and that two different regions of the beta subunits were labeled, centered on beta-Tyr-345 in the case of 2-azido[3H]ADP [Garin, J., Boulay, F., Issartel, J.P., Lunardi, J., & Vignais, P. V. (1986) Biochemistry 25, 4431-4437] and beta-Tyr-311 that of 8-azido[3H]ADP [Hollemans, M., Runswick, M., Fearnley, I.H., & Walker, J.E. (1983) J. Biol. Chem. 258, 9307-9313].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Photolabeling of mitochondrial F1-H+ATPase by 2-azido[3H]ADP and 8-azido[3H]ADP entrapped as fluorometal complexes into the catalytic sites of the enzyme. 814 78