title: Structure-Based Mechanism for Oxidative Decarboxylation Reactions Mediated by Amino Acids and Heme Propionates in Coproheme Decarboxylase (HemQ).
abstract: Coproheme decarboxylase catalyzes two sequential oxidative decarboxylations with H2O2as 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 CO2products. 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.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: Arianna I
authors.initials: AI
authors.lastname: Celis
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: George H
authors.initials: GH
authors.lastname: Gauss
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: Bennett R
authors.initials: BR
authors.lastname: Streit
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: Krista
authors.initials: K
authors.lastname: Shisler
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: Garrett C
authors.initials: GC
authors.lastname: Moraski
authors.affiliation: Department of Chemistry and Biochemistry, North Dakota State University , Fargo, North Dakota 58108-6050, United States.
authors.forename: Kenton R
authors.initials: KR
authors.lastname: Rodgers
authors.affiliation: Department of Chemistry and Biochemistry, North Dakota State University , Fargo, North Dakota 58108-6050, United States.
authors.forename: Gudrun S
authors.initials: GS
authors.lastname: Lukat-Rodgers
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Peters
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717-3400, United States.
authors.forename: Jennifer L
authors.identifier: 0000-0001-5593-3391
authors.initials: JL
authors.lastname: DuBois
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003653:Decarboxylation; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: D000596:Amino Acids; D002262:Carboxy-Lyases