Structural perturbations of substrate binding and oxidation state changes in a lytic polysaccharide monooxygenase.
Structural perturbations of substrate binding and oxidation state changes in a lytic polysaccharide monooxygenase.
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DOI：
10.1007/s00775-022-01966-z
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发表时间：
2022-12
影响因子：
3
通讯作者：
Davies, Gideon J.
中科院分区：
文献类型：
--
作者：
Walton, Paul H.;Davies, Gideon J.
LPMOs是催化多糖中C-H键氧化的酶，导致其氧化裂解。为了实现这一目标，LPMOs采用高活性氧化中间体，其产生可能与底物结合酶相结合。这种耦合的性质是未知的。在这里，我们报告了在相同空间群中结晶但在不同氧化和底物结合状态下的AA9 LPMO的四个三维结构的统计比较，以确定在氧化状态改变或底物结合时酶会发生哪些显著的结构扰动。在一个新颖的步骤中，我们使用矩量法确定与原子位置坐标相关的全局随机误差，以确定不同结构中单个原子的成对均方根差的高斯分布的统计估计。结果表明，铜氧化态的变化不会导致显著的结构变化，底物的结合只会导致色氨酸残基构象的单一变化。该色氨酸先前已被确定为活性位点和蛋白质外表面之间电荷转移途径的一部分，本文确定的结构变化可能是底物-酶偶联机制的一部分。在线版本包含补充材料，可在10.1007/s00775-022-01966-z获得。
LPMOs are enzymes which catalyse the oxidation of a C-H bond within polysaccharides, leading to their oxidative cleavage. To achieve this, LPMOs employ highly reactive oxidising intermediates, the generation of which is likely coupled to substrate binding to the enzyme. The nature of this coupling is unknown. Here we report a statistical comparison for four three-dimensional structures of an AA9 LPMO crystallised in the same space group but in different oxidation and substrate-binding states, to determine which significant structural perturbations occur at the enzyme upon either oxidation state change or the binding of substrate. In a novel step, we determine the global random error associated with the positional coordinates of atoms using the method of moments to ascertain the statistical estimators of Gaussian distributions of pairwise RMS differences between individual atoms in different structures. The results show that a change in the oxidation state of the copper leads to no significant structural changes, and that binding of the substrate leads to a single change in the conformation of a tryptophan residue. This tryptophan has previously been identified as part of a charge transfer pathway between the active site and the external surface of the protein, and the structural change identified herein may be part of the substrate-enzyme coupling mechanism. The online version contains supplementary material available at 10.1007/s00775-022-01966-z.
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影响因子：
7.8
作者：
Cragg SM;Beckham GT;Bruce NC;Bugg TD;Distel DL;Dupree P;Etxabe AG;Goodell BS;Jellison J;McGeehan JE;McQueen-Mason SJ;Schnorr K;Walton PH;Watts JE;Zimmer M
通讯作者：
Zimmer M
影响因子：
15
作者：
Hemsworth, Glyn R.;Taylor, Edward J.;Kim, Robbert Q.;Gregory, Rebecca C.;Lewis, Sally J.;Turkenburg, Johan P.;Parkin, Alison;Davies, Gideon J.;Walton, Paul H.
通讯作者：
Walton, Paul H.
影响因子：
4
作者：
Phillips, Christopher M.;Beeson, William T.;Marletta, Michael A.
通讯作者：
Marletta, Michael A.
影响因子：
15
作者：
Paradisi, Alessandro;Johnston, Esther M.;Walton, Paul H.
通讯作者：
Walton, Paul H.
影响因子：
12.9
作者：
Wang, Binju;Walton, Paul H.;Rovira, Carme
通讯作者：
Rovira, Carme