Binding of the inhibitor protein IF(1) to bovine F(1)-ATPase.
Binding of the inhibitor protein IF(1) to bovine F(1)-ATPase.
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DOI：
10.1016/j.jmb.2010.12.025
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发表时间：
2011-02-25
影响因子：
5.6
通讯作者：
Walker JE
中科院分区：
文献类型：
--
作者：
Bason JV;Runswick MJ;Fearnley IM;Walker JE
在被牛抑制蛋白IF 1的1-60位残基抑制的牛F1-ATPase结构中，α-螺旋抑制剂与F1-ATPase的9个亚基中的5个相互作用。为了了解单个氨基酸残基对这种复杂结合模式的贡献，引入了N-末端缺失和点突变，并检查了每个突变抑制剂蛋白的结合特性。IF 1的N-末端区域使抑制剂与F1-ATP酶的相互作用不稳定，并且当F1 Fo-ATP酶产生ATP时，可能有助于从其结合位点去除抑制剂。结合能由IF 1长α螺旋残基与β DP亚基和β TP亚基C端结构域之间的疏水相互作用以及抑制剂残基E30与β DP亚基C端结构域残基R408之间的盐桥提供。IF 1长α-螺旋中的几个保守的带电氨基酸也是建立抑制活性所必需的，但在最终抑制状态下，它们不与F1-ATP酶接触，而是占据F1-ATP酶中的水腔。它们可能参与了从抑制剂和酶的初始相互作用到结构中观察到的最终抑制复合物的途径，其中两个ATP分子被水解，酶的转子转动两个120°步骤。这些发现有助于从根本上了解抑制剂的功能，并设计新的抑制剂的酶的催化循环的系统分析。
In the structure of bovine F1-ATPase inhibited with residues 1–60 of the bovine inhibitor protein IF1, the α-helical inhibitor interacts with five of the nine subunits of F1-ATPase. In order to understand the contributions of individual amino acid residues to this complex binding mode, N-terminal deletions and point mutations have been introduced, and the binding properties of each mutant inhibitor protein have been examined. The N-terminal region of IF1 destabilizes the interaction of the inhibitor with F1-ATPase and may assist in removing the inhibitor from its binding site when F1Fo-ATPase is making ATP. Binding energy is provided by hydrophobic interactions between residues in the long α-helix of IF1 and the C-terminal domains of the βDP-subunit and βTP-subunit and a salt bridge between residue E30 in the inhibitor and residue R408 in the C-terminal domain of the βDP-subunit. Several conserved charged amino acids in the long α-helix of IF1 are also required for establishing inhibitory activity, but in the final inhibited state, they are not in contact with F1-ATPase and occupy aqueous cavities in F1-ATPase. They probably participate in the pathway from the initial interaction of the inhibitor and the enzyme to the final inhibited complex observed in the structure, in which two molecules of ATP are hydrolysed and the rotor of the enzyme turns through two 120° steps. These findings contribute to the fundamental understanding of how the inhibitor functions and to the design of new inhibitors for the systematic analysis of the catalytic cycle of the enzyme.
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影响因子：
2.9
作者：
Corvest, Vincent;Sigalat, Claude;Haraux, Francis
通讯作者：
Haraux, Francis
DOI：
10.1016/0005-2728(88)90051-5
发表时间：
1988-03-30
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
LIPPE, G;SORGATO, MC;HARRIS, DA
通讯作者：
HARRIS, DA
DOI：
10.1038/nsb966
发表时间：
2003-09-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Cabezón, E;Montgomery, MG;Walker, JE
通讯作者：
Walker, JE
影响因子：
4.8
作者：
Cabezon, E;Butler, PJG;Walker, JE
通讯作者：
Walker, JE
影响因子：
11.4
作者：
Cabezón, E;Runswick, MJ;Walker, JE
通讯作者：
Walker, JE