Structure-Based Mechanism for Oxidative Decarboxylation Reactions Mediated by Amino Acids and Heme Propionates in Coproheme Decarboxylase (HemQ)

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• 作者：Arianna I. Celis ; George H. Gauss ; Bennett R. Streit ; Krista Shisler ; Garrett C. Moraski ; Kenton R. Rodgers ; Gudrun S. Lukat-Rodgers ; John W. Peters ; Jennifer L. DuBois
• 刊名：Journal of the American Chemical Society
• 出版年：2017
• 出版时间：February 8, 2017
• 年：2017
• 卷：139
• 期：5
• 页码：1900-1911
• 全文大小：773K
• ISSN：1520-5126

文摘

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 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 suggested 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 extended relay of heme-mediated e^–/H⁺ transfers and a novel route for the conversion of carboxylic acids to alkenes.