Electron transfer in genetically engineered proteins. The cytochrome c paradigm

Mauk, A. Grant

doi:10.1007/3-540-53260-9_5

Cited by 30 publications

(1 citation statement)

References 125 publications

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“…Thus, although these four conserved residues are not implicated in ET, their interactions are crucial for structure and stability, including preservation of the hydrophobicity of the heme pocket. Moreover, F10 has been implicated in the recognition of the HCCS enzyme, thus pointing out the importance of these residues in assembly and folding of the protein to the native state. ,,− W59 is H-bonded to one of the heme propionates, which along with the hydrophobic character of its side chain is thought to strongly modulate the electrostatic environment of the heme. , Y67 participates in an extensive redox-sensitive H-bonding network that includes a water molecule and the side chains of N52, T78, and the axial ligand M80. − ,, These interactions are regarded as important determinants of the redox potential and ET reorganization energy of cyt c . ,,− Moreover, Y67 is considered crucial in tertiary structure stabilization as it participates in H-bonds that interconnect loops 40–57 and 71–85, which are involved in pH-dependent and other conformational changes relevant to the apoptotic function. ,,− F82 is a conserved surface residue located in the region of interaction with partner redox proteins but also in close proximity to the heme and, therefore, has been implicated in modulating the redox potential and in establishing efficient interprotein ET pathways. ,, The highly conserved prolines 30, 71, and 76 are thought to play important structural roles. P30 is important in stabilizing the distal H18 ligand; P71 helps to position the proximal ligand M80 and contributes to shield the heme group from the bulk solvent. − T78, also a conserved residue, participates in a H-bonding network that is important for determining the heme environment .…”

Section: Architecture Of Cytochrome Cmentioning

confidence: 99%

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog

et al. 2017

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Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions, and cellular localization, different conformations may be stabilized, which differ in structure, redox properties, binding affinities, and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt c in the intermembrane mitochondrial space of healthy cells. Under pro-apoptotic conditions, however, cyt c gains cardiolipin peroxidase activity, translocates into the cytosol to engage in the intrinsic apoptotic pathway, and enters the nucleus where it impedes nucleosome assembly. Other reported functions include cytosolic redox sensing and involvement in the mitochondrial oxidative folding machinery. Moreover, post-translational modifications such as nitration, phosphorylation, and sulfoxidation of specific amino acids induce alternative conformations with differential properties, at least in vitro. Similar structural and functional alterations are elicited by biologically significant electric fields and by naturally occurring mutations of human cyt c that, along with mutations at the level of the maturation system, are associated with specific diseases. Here, we summarize current knowledge and recent advances in understanding the different structural, dynamic, and thermodynamic factors that regulate the primary electron transfer function, as well as alternative functions and conformations of cyt c. Finally, we present recent technological applications of this moonlighting protein.

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Section: Architecture Of Cytochrome Cmentioning

confidence: 99%

Multifunctional Cytochrome c: Learning New Tricks from an Old Dog

et al. 2017

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Iron Porphyrin Chemistry

Walker¹,

Simonis²

2005

Encyclopedia of Inorganic Chemistry

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This article reviews most aspects of the chemistry of iron porphyrins, from Fe(0) to Fe(V), including occurrence and roles of natural iron porphyrins (hemes) and their synthetic analogs, structures and electron configurations of iron porphyrins of all oxidation and spin states, π electron configuration of the porphyrin ring, synthesis of metal‐free porphyrins and other related macrocycles, insertion of iron into free‐base porphyrins and related macrocycles, the properties, reactions, uses and biological relevance of iron(0), ‐(I), ‐(II) porphyrins (the latter with S = 0, 1, and 2 spin state possibilities), of iron(II) porphyrin π‐cation radicals, of iron(III) porphyrins (with S = 1/2, 3/2, and 5/2 spin state possibilities), of iron(III) porphyrin and corrole π‐cation radicals, of iron(IV) porphyrins (including five‐ and six‐coordinate ferryl (FeO) 2+ , iron(IV) phenyl, carbene and hydrazine complexes, and the bis‐methoxide complex) and a comparison of iron(IV) porphyrins to iron(III) porphyrin π‐cation radicals, of iron(IV) porphyrin π‐cation radicals, and of the possible existence of iron(V) porphyrins. Included in the Fe(II) part are sections on addition of ligands to four‐coordinate iron(II) porphyrins, including equilibrium binding constants, photodissociation of ligands from PFeL 2 complexes, binding of small molecules (O 2 , CO, NO, HNO) to 5‐coordinate iron(II) porphyrins and design of porphyrin ligands that will mimic the active sites of heme proteins such as myoglobin and hemoglobin, the cytochromes P450 and nitric oxide synthases, and the nitrophorins and guanylyl cyclases. Included in the iron(III) part are sections on both 5‐ and 6‐coordinate high‐spin complexes and their similarities and differences, bridged or through‐space magnetically coupled complexes of high‐spin iron(III) porphyrins with other metal complexes as possible models for cytochrome oxidase and the assimilatory sulfite reductases, coupled oxidation of hemes by hydrogen peroxide or its equivalent, and the relationship of this reactivity to the reactions of heme oxygenase, iron(III) porphyrins as reduction catalysts, and photochemistry of iron(III) porphyrins, possible electron configurations of low‐spin iron(III) porphyrins, the phenomenon and possible electronic consequences of ruffling of the porphinato core in iron(III) porphyrins, the preferred orientation of planar axial ligands bound to low‐spin iron(III) porphyrins, NO complexes of iron(III) porphyrins, reduction potentials, equilibrium constants and rates of axial‐ligand addition and exchange, kinetics of axial‐ligand rotation and porphyrin ring inversion, kinetics of reduction and autoreduction of iron(III) porphyrins, electron self‐exchange between low‐spin iron(III) and iron(II) porphyrins, synthetic ferriheme proteins, and synthesis of five‐coordinate low‐spin iron(III) porphyrins having σ‐alkyl or σ‐aryl groups as axial ligands. The iron(IV) and iron(IV) cation radical sections discuss the high‐valent states of cytochromes P450 and related enzymes.

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