A Structure‐Based Mechanism for Oxidative Decarboxylation Reactions Mediated by Amino Acids and Heme Propionates
A Structure‐Based Mechanism for Oxidative Decarboxylation Reactions Mediated by Amino Acids and Heme Propionates
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氨基酸和丙酸血红素介导的基于结构的氧化脱羧反应机制
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发表时间：
2017
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通讯作者：
Arianna I. Celis
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作者：
Arianna I. Celis
粪血红素脱羧酶以H2 O2为氧化剂，粪血红素III为底物和辅因子，血红素B为产物，催化两个连续的氧化脱羧。每个反应都会破坏一个C-C键，并通过不清楚的步骤导致氢化物的净损失。与底物类似物复合的蛋白质的溶液和固态结构表征揭示了高度非常规的H2 O2活化远端环境，其中反应性丙酸（2和4）位于卟啉平面的相对侧。这表明，与高价铁中间体催化的直接C-H键裂解相反，粪血红素氧化必须通过介导氨基酸残基发生。一个酪氨酸，氢键丙酸2在一个位置类似于在抗坏血酸过氧化物酶的底物是必不可少的两个脱羧，而赖氨酸盐桥丙酸4只需要为第二。提出了一种机制，其中丙酸酯2将氧化当量从粪血红素化合物I中间体传递到反应性去质子化酪氨酸，形成Tyr。然后，该残基从丙酸酯2中夺取一个净氢原子（H■），然后将未配对的丙酰基电子迁移到粪血红素铁上，产生铁的硬血红素和CO2产物。一个类似的途径提出了丙酸4的脱羧，但与赖氨酸残基作为一个必不可少的质子穿梭。提出的反应表明血红素介导的e−/H+转移的前所未有的中继和羧酸转化为烯烃的新途径。
Coproheme decarboxylase catalyzes two sequential oxidative decarboxylations with H2O2 as the oxidant, coproheme III as substrate and cofactor, and heme b as the product. Each reaction breaks a C‐C bond and results in net loss of hydride, via steps that are not clear. Solution and solid‐state structural characterization of the protein in complex with a substrate analog has revealed a highly unconventional H2O2‐activating distal environment with the reactive propionic acids (2 and 4) on the opposite side of the porphyrin plane. This suggests that, in contrast to direct C‐H bond cleavage catalyzed by a high‐valent iron intermediate, the coproheme oxidations must occur through mediating amino acid residues. A tyrosine that hydrogen bonds to propionate 2 in a position analogous to the substrate in ascorbate peroxidase is essential for both decarboxylations, while a lysine that salt bridges to propionate 4 is required solely for the second. A mechanism is proposed in which propionate 2 relays an oxidizing equivalent from a coproheme compound I intermediate to the reactive deprotonated tyrosine, forming Tyr■. This residue then abstracts a net hydrogen atom (H■) from propionate 2, followed by migration of the unpaired propionyl electron to the coproheme iron to yield the ferric harderoheme and CO2 products. A similar pathway is proposed for decarboxylation of propionate 4, but with a lysine residue as an essential proton shuttle. The proposed reaction suggests an unprecedented relay of heme‐mediated e−/H+ transfers and a novel route for the conversion of carboxylic acids to alkenes.