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Molecular mechanism of lytic polysaccharide monooxygenases†
Chemical Science ( IF 7.6 ) Pub Date : 2018-03-26 00:00:00 , DOI: 10.1039/c8sc00426a Erik Donovan Hedegård 1 , Ulf Ryde 1
Chemical Science ( IF 7.6 ) Pub Date : 2018-03-26 00:00:00 , DOI: 10.1039/c8sc00426a Erik Donovan Hedegård 1 , Ulf Ryde 1
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The lytic polysaccharide monooxygenases (LPMOs) are copper metalloenzymes that can enhance polysaccharide depolymerization through an oxidative mechanism and hence boost generation of biofuel from e.g. cellulose. By employing density functional theory in a combination of quantum mechanics and molecular mechanics (QM/MM), we report a complete description of the molecular mechanism of LPMOs. The QM/MM scheme allows us to describe all reaction steps with a detailed protein environment and we show that this is necessary. Several active species capable of abstracting a hydrogen from the substrate have been proposed previously and starting from recent crystallographic work on a substrate–LPMO complex, we investigate previously suggested paths as well as new ones. We describe the generation of the reactive intermediates, the abstraction of a hydrogen atom from the polysaccharide substrate, as well as the final recombination step in which OH is transferred back to the substrate. We show that a superoxo [CuO2]+ complex can be protonated by a nearby histidine residue (suggested by recent mutagenesis studies and crystallographic work) and, provided an electron source is available, leads to formation of an oxyl-complex after cleavage of the O–O bond and dissociation of water. The oxyl complex either reacts with the substrate or is further protonated to a hydroxyl complex. Both the oxyl and hydroxyl complexes are also readily generated from a reaction with H2O2, which was recently suggested to be the true co-substrate, rather than O2. The C–H abstraction by the oxyl and hydroxy complexes is overall favorable with activation barriers of 69 and 94 kJ mol−1, compared to the much higher barrier (156 kJ mol−1) obtained for the copper–superoxo species. We obtain good structural agreement for intermediates for which structural data are available and the estimated reaction energies agree with experimental rate constants. Thus, our suggested mechanism is the most complete to date and concur with available experimental evidence.
中文翻译：
裂解多糖单加氧酶的分子机制†
裂解多糖单加氧酶（LPMO）是铜金属酶，可以通过氧化机制增强多糖解聚，从而促进从纤维素等生物燃料的生成。通过结合量子力学和分子力学（QM/MM）采用密度泛函理论，我们报告了 LPMO 分子机制的完整描述。 QM/MM 方案允许我们用详细的蛋白质环境描述所有反应步骤，并且我们证明这是必要的。之前已经提出了几种能够从基底中提取氢的活性物质，并且从最近对基底-LPMO复合物的晶体学工作开始，我们研究了之前建议的路径以及新的路径。我们描述了反应中间体的生成、从多糖底物中提取氢原子，以及 OH 转移回底物的最终重组步骤。我们表明，超氧[CuO 2 ] +复合物可以被附近的组氨酸残基质子化（最近的诱变研究和晶体学工作表明），并且如果有可用的电子源，则在裂解后导致形成氧复合物。 O-O键和水的解离。氧基络合物或者与底物反应或者进一步质子化成羟基络合物。氧基和羟基络合物也很容易通过与 H 2 O 2的反应生成，最近有人认为 H 2 O 2 而非 O 2才是真正的共底物。 与铜-超氧物质获得的更高的势垒（156 kJ mol -1 ）相比，氧基和羟基络合物的C-H提取总体上是有利的，活化势垒为69和94 kJ mol -1 。我们获得了中间体的良好结构一致性，其中结构数据可用，并且估计的反应能量与实验速率常数一致。因此，我们提出的机制是迄今为止最完整的，并且与现有的实验证据一致。
更新日期：2018-03-26
中文翻译：
裂解多糖单加氧酶的分子机制†
裂解多糖单加氧酶（LPMO）是铜金属酶，可以通过氧化机制增强多糖解聚，从而促进从纤维素等生物燃料的生成。通过结合量子力学和分子力学（QM/MM）采用密度泛函理论，我们报告了 LPMO 分子机制的完整描述。 QM/MM 方案允许我们用详细的蛋白质环境描述所有反应步骤，并且我们证明这是必要的。之前已经提出了几种能够从基底中提取氢的活性物质，并且从最近对基底-LPMO复合物的晶体学工作开始，我们研究了之前建议的路径以及新的路径。我们描述了反应中间体的生成、从多糖底物中提取氢原子，以及 OH 转移回底物的最终重组步骤。我们表明，超氧[CuO 2 ] +复合物可以被附近的组氨酸残基质子化（最近的诱变研究和晶体学工作表明），并且如果有可用的电子源，则在裂解后导致形成氧复合物。 O-O键和水的解离。氧基络合物或者与底物反应或者进一步质子化成羟基络合物。氧基和羟基络合物也很容易通过与 H 2 O 2的反应生成，最近有人认为 H 2 O 2 而非 O 2才是真正的共底物。 与铜-超氧物质获得的更高的势垒（156 kJ mol -1 ）相比，氧基和羟基络合物的C-H提取总体上是有利的，活化势垒为69和94 kJ mol -1 。我们获得了中间体的良好结构一致性，其中结构数据可用，并且估计的反应能量与实验速率常数一致。因此，我们提出的机制是迄今为止最完整的，并且与现有的实验证据一致。
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