INHIBITION OF H+-TRANSPORTING ATPASE BY FORMATION OF A TIGHT NUCLEOSIDE DIPHOSPHATE FLUOROALUMINATE COMPLEX AT THE CATALYTIC SITE
INHIBITION OF H+-TRANSPORTING ATPASE BY FORMATION OF A TIGHT NUCLEOSIDE DIPHOSPHATE FLUOROALUMINATE COMPLEX AT THE CATALYTIC SITE
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DOI：
10.1073/pnas.85.23.8958
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发表时间：
1988-12-01
影响因子：
11.1
通讯作者：
VIGNAIS, PV
中科院分区：
文献类型：
--
作者：
LUNARDI, J;DUPUIS, A;VIGNAIS, PV
发现氟化物对线粒体和细菌F1型ATP酶[ATP磷酸水解酶（H+-转运），EC 3.6.1.34]的抑制依赖于F1型ATP酶催化位点处铝和ADP的存在。AlF_4 ~-被证明是活性氟铝酸盐物种。在ADP和NaF存在下，铍（一种形成严格四配位的氟化物络合物的金属）对F1型ATP酶活性的抑制作用相同，表明铝通过四面体络合物起作用。在ADP存在下，AlF 4-对分离的F1型ATP酶的抑制不能被ADP、ATP或铝的螯合剂逆转。然而，抑制的ATP酶活性的F1部门在submitochondrial颗粒所造成的AlF 4-和ADP被逆转后，添加可氧化的底物。解偶联剂阻止抑制的逆转，这表明呼吸产生的质子动力是负责抑制的缓解。由于AlF 4-和PO 43-之间的结构相似性，推测AlF 4-模拟ATP的磷酸基团，并在F1型ATP酶的活性位点与ADP形成失败的复合物。
Inhibition of the mitochondrial and bacterial F1-type ATPases [of ATP phosphohydrolase (H+-transporting), EC 3.6.1.34] by fluoride was found to depend on the presence of aluminum and ADP at the catalytic site(s) of F1-type ATPase. AlF4- was demonstrated to be the active fluoroaluminate species. The identical pattern of inhibition of F1-type ATPase activity obtained in the presence of ADP and NaF with beryllium, a metal that forms fluoride complexes strictly tetracoordinated, suggests that aluminum acts through a tetrahedral complex. Inhibition of isolated F1-type ATPase by AlF4- in the presence of ADP cannot be reversed by ADP, ATP, or chelators of aluminum. However, the inhibition of the ATPase activity of the F1 sector in submitochondrial particles caused by AlF4- and ADP was reversed upon addition of an oxidizable substrate. Uncouplers prevented the reversal of inhibition, suggesting that the protonmotive force generated by respiration was responsible for the relief of inhibition. Because of structural similarities between AlF4- and PO43-, AlF4- is postulated to mimic the phosphate group of ATP and form an abortive complex with ADP at the active site(s) of F1-type ATPase.