A Functional Model of the Cytochrome c Oxidase Active Site: Unique Conversion of a Heme–μ‐peroxo–CuII Intermediate into Heme– superoxo/CuI

Liu, Jingang; Naruta, Yoshinori; Tani, Fumito

doi:10.1002/ange.200462582

Cited by 17 publications

(13 citation statements)

References 55 publications

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“…A more complete CcO model was realized by the introduction of an axial imidazole ligand and a cross-linked tyrosine unit. [15] A m-h 2 /h 2 -mode peroxo ligand is realized at the Fe/Cu center of a bis(2-pyridylmethyl)amine unit that is covalently connected to a F 6 -porphyrin. [16,17] Iron porphyrins may also be noncovalently juxtaposed to copper centers, and this motif also activates dioxygen.…”

Section: Introductionmentioning

confidence: 99%

Terpyridine–Porphyrin Hetero‐Pacman Compounds

Schwalbe

Metzinger

Teets

et al. 2012

Chemistry A European J

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The two different coordination spheres afforded by Pacman architectures offer cooperativity derived from two different metal centers. A modular strategy is developed to produce a hetero-Pacman scaffold featuring a porphyrin and terpyridine for metal-ion binding. A double Suzuki reaction was employed to first attach a terpyridine moiety to a xanthene backbone and then attach a porphyrin. The new hetero-Pacman scaffold has been characterized and all building blocks have been isolated and structurally characterized. The principle objective to incorporate different metal centers was confirmed by isolating a trinuclear complex comprising two porphyrinic units and a bis(terpyridine)-iron unit. The compounds described herein expand the Pacman scaffold concept by allowing for the incorporation of a terpyridine-metal complex proximate to a porphyrin-cofactor active site for small-molecule activation.

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Section: Introductionmentioning

confidence: 99%

Terpyridine–Porphyrin Hetero‐Pacman Compounds

Schwalbe

Metzinger

Teets

et al. 2012

Chemistry A European J

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“…Despite these successes, the roles of the conserved glutamates and metal ions still remain to be fully elucidated, partly because of the difficulty in obtaining native NOR in high yield and the lack of a 3D structure. Even if these problems are resolved, it is still difficult to replace iron in the native Fe B site with other metal ions, and spectroscopic studies of native NOR are often complicated by the presence of other metal cofactors (e.g., low-spin heme).To overcome these limitations, a number of synthetic models of NOR using small organic molecules as ligands, have been made in which the nonheme Fe B site can be replaced by a copper ion (17,(38)(39)(40)(41)(42)(43)(44)(45). In addition, since these model systems lack additional metal-binding sites, spectroscopic studies are often simplified.…”

mentioning

confidence: 99%

“…To overcome these limitations, a number of synthetic models of NOR using small organic molecules as ligands, have been made in which the nonheme Fe B site can be replaced by a copper ion (17,(38)(39)(40)(41)(42)(43)(44)(45). In addition, since these model systems lack additional metal-binding sites, spectroscopic studies are often simplified.…”

mentioning

confidence: 99%

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

Lin

Yeung²,

Gao³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

108

140

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A structural and functional model of bacterial nitric oxide reductase (NOR) has been designed by introducing two glutamates (Glu) and three histidines (His) in sperm whale myoglobin. X-ray structural data indicate that the three His and one Glu (V68E) residues bind iron, mimicking the putative Fe B site in NOR, while the second Glu (I107E) interacts with a water molecule and forms a hydrogen bonding network in the designed protein. Unlike the first Glu (V68E), which lowered the heme reduction potential by ∼110 mV, the second Glu has little effect on the heme potential, suggesting that the negatively charged Glu has a different role in redox tuning. More importantly, introducing the second Glu resulted in a ∼100% increase in NOR activity, suggesting the importance of a hydrogen bonding network in facilitating proton delivery during NOR reactivity. In addition, EPR and X-ray structural studies indicate that the designed protein binds iron, copper, or zinc in the Fe B site, each with different effects on the structures and NOR activities, suggesting that both redox activity and an intermediate five-coordinate heme-NO species are important for high NOR activity. The designed protein offers an excellent model for NOR and demonstrates the power of using designed proteins as a simpler and more welldefined system to address important chemical and biological issues.biomimetic models | heme-copper oxidase | metalloprotein | protein design | protein engineering R ational design of proteins that mimic both structure and function of more complex native enzymes has been a long soughtafter goal, as the process is an ultimate test of our knowledge and an excellent means to develop advanced biocatalysts (1-3). Although designed proteins that model the structure of native enzymes have been known for a while (4-10), successful designs of proteins that mimic both the structure and function of native enzymes have been reported only recently (11-16). While being able to design such functional proteins is laudable, the impact of such an achievement would be greater if the designed proteins can be used to address fundamental issues in chemistry and biology that are difficult to tackle by other methods. One primary example is the roles of conserved glutamates and metal ions in bacterial nitric oxide reductase (NOR) (17)(18)(19).NO is critical for all life (20). Bacterial denitrification is a crucial part of the nitrogen cycle in nature that involves a four-step, five-electron reduction of nitrate (NO 3 − ) to dinitrogen (N 2 ) (17, 19). Bacterial NOR is a membrane-bound protein that catalyzes one step of this process, namely, the two-electron reduction of NO to N 2 O (17, 19). With no crystal or solution structure available for bacterial NOR to date, sequence alignments and homology modeling (21, 22) have indicated that NOR is structurally homologous to the largest subunit (subunit I) of hemecopper oxidases (HCOs) (23), enzymes that catalyze reduction of O 2 to water. The active sites of both NOR and HCO contain a proximal histidine-coo...

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“…The values of the OÀO vibrations are comparable to those seen in previously reported heme-peroxocopper models possessing a tetradentate Cu-chelate moiety (Table 1). [10,12,15,16] The fact that the O À O vibration frequencies of the peroxides formed by the free hydroxy model 1 a and the protected hydroxy model 1 b are almost identical suggests that interactions of the phenol moiety with the peroxide group are insignificant if they do occur.…”

Section: A C H T U N G T R E N N U N G (Tmp)]mentioning

confidence: 94%

“…[11] The resultant heme/copper compound reacts with dioxygen to form a peroxide species that is stable at low temperature. In a very recent paper [12] we described a fully integrated CcO model (L To refine our model of the CcO tridentate (His) 2 Cu B A C H T U N G T R E N N U N G (HisTyr) site further and to obtain further insights into the dioxygen reduction mechanism, we prepared [(L Figure 2), which represents a new example of a covalently tethered heme/Cu CcO model bearing a tridentate N3-copper chelate with a moiety acting as a crosslinked His-Tyr mimic. The oxygenation reaction of the N3-copper chelate heme/copper model compound produces a heme superoxide intermediate in nitrile solvents, while in CH 2 Cl 2 / 7 % EtCN the coexistence of a heme superoxide and a bridged heme-O 2 -Cu peroxide species in equivalent amounts is observed.…”

Section: H T U N G T R E N N U N G (Tmp)]mentioning

confidence: 98%

Synthetic Models of the Active Site of Cytochrome c Oxidase: Influence of Tridentate or Tetradentate Copper Chelates Bearing a HisTyr Linkage Mimic on Dioxygen Adduct Formation by Heme/Cu Complexes

Liu

Naruta

Tani

2007

Chemistry A European J

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Two synthetic models of the active site of cytochrome c oxidase--[(LN4-OH)CuI-FeII(TMP)]+ (1 a) and [(LN3-OH)CuI-FeII(TMP)]+ (2 a)-have been designed and synthesized. These models each contain a heme and a covalently attached copper moiety supported either by a tetradentate N4-copper chelate or by a tridentate N3-copper chelate including a moiety that acts as a mimic of the crosslinked His-Tyr component of cytochrome c oxidase. Low-temperature oxygenation reactions of these models have been investigated by spectroscopic methods including UV/Vis, resonance Raman, ESI-MS, and EPR spectroscopy. Oxygenation of the tetradentate model 1 a in MeCN and in other solvents produces a low-temperature-stable dioxygen-bridged peroxide [(LN4-OH)CuII-O2-FeIII(TMP)]+ {nuO--O=799 (16O2)/752 cm(-1) (18O2)}, while a heme superoxide species [(TMP)FeIII(O2-)CuIILN3-OH] {nuFe--O2: 576 (16O2)/551 cm(-1) (18O2)} is generated when the tridentate model 2 a is oxygenated in EtCN solution under similar experimental conditions. The coexistence of a heme superoxide species [(TMP)FeIII(O2-)CuIILN3-OH] and a bridged peroxide [(LN3-OH)CuII-O2-FeIII(TMP)]+ species in equal amounts is observed when the oxygenation reaction of 2 a is performed in CH2Cl(2)/7 % EtCN, while the percentage of the peroxide (approximately 70 %) in relation to superoxide (approximately 30 %) increases further when the crosslinked phenol moiety in 2 a is deprotonated to produce the bridged peroxide [(LN3-OH)CuII-O2-FeIII(TMP)]+ {nuO--O: 812 (16O2)/765 cm(-1) (18O2)} as the main dioxygen intermediate. The weak reducibility and decreased O2 reactivity of the tricoordinated CuI site in 2 a are responsible for the solvent-dependent formation of dioxygen adducts. The initial binding of dioxygen to the copper site en route to the formation of a bridged heme-O2-Cu intermediate by model 2 a is suggested and the deprotonated crosslinked His-Tyr moiety might contribute to enhancement of the O2 affinity of the CuI site at an early stage of the dioxygen-binding process.

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A Functional Model of the Cytochrome c Oxidase Active Site: Unique Conversion of a Heme–μ‐peroxo–Cu^II Intermediate into Heme– superoxo/Cu^I

Cited by 17 publications

References 55 publications

Terpyridine–Porphyrin Hetero‐Pacman Compounds

Terpyridine–Porphyrin Hetero‐Pacman Compounds

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

Synthetic Models of the Active Site of Cytochrome c Oxidase: Influence of Tridentate or Tetradentate Copper Chelates Bearing a HisTyr Linkage Mimic on Dioxygen Adduct Formation by Heme/Cu Complexes

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