Theory and Practice of Electron Transfer within Protein−Protein Complexes:  Application to the Multidomain Binding of Cytochrome<i>c</i>by Cytochrome<i>c</i>Peroxidase

Nocek, Judith M.; Zhou, Junhu; Forest, Sarah De; Priyadarshy, Satyam; Beratan, David N.; Onuchic, José N.; Hoffman, Brian M.

doi:10.1021/cr9500444

Cited by 195 publications

(252 citation statements)

References 160 publications

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“…Ccp catalyzes the two-electron reduction of H 2 O 2 by ferrocyt c. Peroxide reacts rapidly with the resting ferric form of ccp to produce a species referred to as compound I, which contains a ferryl [Fe(IV)O 2ϩ ] heme and a protein radical located on Trp-191. The ET reactions involving these physiological redox partners have been studied in great detail (77). At low ionic strength, acidic ccp and basic cyt c form a stable complex.…”

Section: Protein-protein Reactionsmentioning

confidence: 99%

“…Results from quenching studies, temperature and ionic strength dependences, species variations, and electrostatic modeling provide compelling evidence for two distinct cyt c binding sites on ccp. The higher-affinity binding site is the locus for Trp-191 radical reduction by cyt c. Heme (ccp) reduction by cyt c can occur from either the high-or lowaffinity binding site but, when exchange between the two is rapid, reduction from the low-affinity site dominates (77). These studies of ccp͞cyt c and cyt b 5 ͞c ET, including an important contribution by Hoffman and coworkers (79) in this issue of PNAS, have shed much light on the mechanisms of protein-protein ET processes.…”

Section: Protein-protein Reactionsmentioning

confidence: 99%

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Long-range electron transfer

Gray

Winkler

2005

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

743

836

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Recent investigations have shed much light on the nuclear and electronic factors that control the rates of long-range electron tunneling through molecules in aqueous and organic glasses as well as through bonds in donor-bridge-acceptor complexes. Couplings through covalent and hydrogen bonds are much stronger than those across van der Waals gaps, and these differences in coupling between bonded and nonbonded atoms account for the dependence of tunneling rates on the structure of the media between redox sites in Ru-modified proteins and protein-protein complexes.electron tunneling ͉ hopping ͉ glass ͉ protein

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Section: Protein-protein Reactionsmentioning

confidence: 99%

Section: Protein-protein Reactionsmentioning

confidence: 99%

Long-range electron transfer

Gray

Winkler

2005

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

743

836

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“…systems (1)(2)(3)(4)(5)(6) for the creation of artificial catalysis and bioelectronics devices for novel biosensors is a challenging objective (7)(8)(9). Several researchers have made significant advances in construction of artificial ET biosystems by chemical modification of native cofactors (10)(11)(12), substrates (13), and enzymes (14).…”

Section: Esign Of Biological Protein-protein Electron Transfer (Et)mentioning

confidence: 99%

Design of metal cofactors activated by a protein–protein electron transfer system

Ueno¹,

Yokoi

Unno

et al. 2006

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

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Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which fundamental understanding is expected to provide a wealth of applications in biotechnology. Investigations of protein-protein ET systems in reductive activation of artificial cofactors introduced into proteins remains particularly challenging because of the complexity of interactions between the cofactor and the system contributing to ET. In this work, we construct an artificial protein-protein ET system, using heme oxygenase (HO), which is known to catalyze the conversion of heme to biliverdin. HO uses electrons provided from NADPH/ cytochrome P450 reductase (CPR) through protein-protein complex formation during the enzymatic reaction. We report that a Fe III (Schiff-base), in the place of the active-site heme prosthetic group of HO, can be reduced by NADPH/CPR. The crystal structure of the Fe(10-CH2CH2COOH-Schiff-base)⅐HO composite indicates the presence of a hydrogen bond between the propionic acid carboxyl group and Arg-177 of HO. Furthermore, the ET rate from NADPH/ CPR to the composite is 3.5-fold faster than that of Fe(Schiffbase)⅐HO, although the redox potential of Fe(10-CH2CH2COOH-Schiff-base)⅐HO (؊79 mV vs. NHE) is lower than that of Fe(Schiffbase)⅐HO (؉15 mV vs. NHE), where NHE is normal hydrogen electrode. This work describes a synthetic metal complex activated by means of a protein-protein ET system, which has not previously been reported. Moreover, the result suggests the importance of the hydrogen bond for the ET reaction of HO. Our Fe(Schiffbase)⅐HO composite model system may provide insights with regard to design of ET biosystems for sensors, catalysts, and electronics devices.heme oxygenase ͉ metalloprotein ͉ protein-protein interaction ͉ schiff-base ͉ hydrogen bond D esign of biological protein-protein electron transfer (ET) systems (1-6) for the creation of artificial catalysis and bioelectronics devices for novel biosensors is a challenging objective (7-9). Several researchers have made significant advances in construction of artificial ET biosystems by chemical modification of native cofactors (10-12), substrates (13), and enzymes (14). For example, Gray and Winkler (6) reported that synthetic light harvesting metal complexes bound to metalloproteins can act as triggers of ET reactions. However, challenges remain for introduction of unnatural molecules into protein scaffolds in design of ET systems because of the challenges in understanding the complex noncovalent interactions contributing to ET processes.Heme oxygenase (HO) is known to catalyze the conversion of heme to biliverdin. HO utilizes electrons provided from a NADPH͞cytochrome P450 reductase (CPR) system (Fig. 1A) (15). The first electron reduces the heme Fe(III) to Fe(II) to initiate the enzymatic reaction, which is followed by a second reduction of O 2 -ligated heme for the hydroxylation of the C ␣ atom of the heme (Fig. 1 A). The electron flow has been proposed to proceed from NADPH to the heme iron atom of the redox partner, HO, v...

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“…We have used these two redox proteins as a model system, with which to investigate and understand electron transfer between proteins. They represent a useful parallel system to the well-studied yeast cytochrome c and yeast CCP [1,2] in that the cytochrome c donors are structurally similar but the peroxidases are quite distinct.Like the yeast peroxidase, the Paracoccus enzyme requires two electrons to restore the active form after oxidation by hydrogen peroxide. In the yeast case, these are probably delivered singly by two ferrocytochrome c molecules sequentially encountering the peroxidase surface.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

The surface‐charge asymmetry and dimerisation of cytochrome c550 from Paracoccus denitrificans @MM implications for the interaction with cytochrome c peroxidase

Pettigrew

Gilmour

Goodhew

et al. 1998

European Journal of Biochemistry

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The implications of the dimeric state of cytochrome c550 for its binding to Paracoccus cytochrome c peroxidase and its delivery of the two electrons required to restore the active enzyme during catalysis have been investigated. The amino acid sequence of cytochrome c550 of Paracoccus denitrificans strain LMD 52.44 was determined and showed 21 differences from that of strain LMD 22.21. Based on the X-ray structure of the latter, a structure for the cytochrome c550 monomer from strain 52.44 is proposed and a dipole moment of 945 debye was calculated with an orientation close to the exposed haem edge. The behaviour of the cytochrome on molecular-exclusion chromatography is indicative of an ionic strength-dependent monomer (15 kDa)/dimer (30 kDa) equilibrium that can also be detected by 1 H-NMR spectroscopy. The apparent mass of 50 kDa observed at very low ionic strength was consistent with the presence of a strongly asymmetric dimer. This was confirmed by cross-linking studies, which showed that a cross-linked species of mass 30 kDa on SDS behaved with an apparent mass of 50 kDa on molecular-exclusion chromatography. A programme which carried out and evaluated molecular docking of two monomers to give a dimer generated a most probable dimer in which the monomer dipoles lay almost antiparallel to each other. The resultant dipole moment of the dimer is therefore small. Although this finding calls into question the possibility of preorientation of a strongly asymmetrically charged cytochrome as it collides with a redox partner, the stoichiometry of complex formation with cytochrome c peroxidase as studied by 1 H-NMR spectroscopy shows that it is the monomer that binds.Keywords : cytochrome; peroxidase ; electron transfer; electrostatic ; dimerisation.Paracoccus denitrificans cytochrome c550 is the electron donor for Paracoccus cytochrome c peroxidase (CCP). We have used these two redox proteins as a model system, with which to investigate and understand electron transfer between proteins. They represent a useful parallel system to the well-studied yeast cytochrome c and yeast CCP [1,2] in that the cytochrome c donors are structurally similar but the peroxidases are quite distinct.Like the yeast peroxidase, the Paracoccus enzyme requires two electrons to restore the active form after oxidation by hydrogen peroxide. In the yeast case, these are probably delivered singly by two ferrocytochrome c molecules sequentially encountering the peroxidase surface. The Paracoccus enzyme contains two haems rather than one, and in separate domains of the protein [3]. One haem is believed to perform an electrontransferring function and the other, a peroxidatic function. With two domains, each carrying an oxidising centre in the intermedi-

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Theory and Practice of Electron Transfer within Protein−Protein Complexes: Application to the Multidomain Binding of Cytochromecby CytochromecPeroxidase

Cited by 195 publications

References 160 publications

Long-range electron transfer

Long-range electron transfer

Design of metal cofactors activated by a protein–protein electron transfer system

The surface‐charge asymmetry and dimerisation of cytochrome c550 from Paracoccus denitrificans @MM implications for the interaction with cytochrome c peroxidase

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