Design, Synthesis, and Circular Dichroism Investigation of a Peptide-Sandwiched Mesoheme

Benson, David R.; Hart, Bradley R.; Zhu, X. X.; Doughty, Michael B.

doi:10.1021/ja00138a002

Cited by 103 publications

(124 citation statements)

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“…[32]. Moreover the g values might be taken as indication that the planes of two axially coordinated imidazoles aligned approximately parallel to one another, confirmed by continuous wave [31,33] as well as by pulsed EPR spectroscopy [34].…”

Section: IIImentioning

confidence: 94%

EPR study of a novel [Fe–porphyrin] catalyst

et al. 2007

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Section: IIImentioning

confidence: 94%

EPR study of a novel [Fe–porphyrin] catalyst

et al. 2007

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“…21,22 In the bovine microsomal holocyt b 5 structure, Ser64 forms two hydrogen bonds with the 7-propionate carboxyl group: one involves the OcH and the other the backbone NH (Figures 2A and 2B). 10,11 The consequences of propionate esterification are consistent with the formation of these H-bonds in solution.…”

Section: Peptide-heme Conjugate Designmentioning

confidence: 99%

“…Mesoheme, rather than heme, was selected for the synthesis because it lacked the potentially reactive vinyl groups of protoporphyrin IX. 22 The control peptide (referred to as BLP-8) spanned Glu59-Asp66 of the cyt b 5 sequence with the Ser64Lys replacement. The test peptide (referred to as BLP-22C 0 ) was created using the 22 C-terminal residues of the cyt b 5 binding loop (Gly52-Thr73) with two alterations: Ser64Lys to provide the desired site of heme attachment and Lys72Xxx to eliminate a second reactive location.…”

Section: Peptide-heme Conjugate Designmentioning

confidence: 99%

Structural propensities in the heme binding region of apocytochrome b₅. II. Heme conjugates

Davis¹,

Lecomte²

2008

Biopolymers

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In the absence of heme cofactor, the water-soluble domain of rat microsomal cytochrome b5 (cyt b5) contains a long flexible region within its 42-residue heme-binding loop. Heme capture induces this region to fold into a well-defined structure containing helices H3-H5, each separated by a turn, with His39 and His63 serving as axial ligands to the heme iron. We have shown that the H4 region of the apoprotein has the greatest tendency for disorder within the isolated binding loop. Here, the effect of the His63-iron bond and proximity of heme plane on the population of helical conformation in H4 and H5 was investigated by synthesis and characterization of a peptide-sandwiched mesoheme construct in which two H4-H5 peptides were covalently attached to a single cofactor. Spectroscopic data indicated that a holoprotein-like bis-histidine coordination state was achieved over a pH range from 7 to 9. Trifluoroethanol titrations of the construct and the analogous free peptide under these pH conditions revealed that heme proximity and iron ligation were insufficient to promote helix formation in H4 and H5. These observations were used to assess the role of disordered regions in heme capture and the loop-scaffold interface in holoprotein folding and stability.

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“…One or two peptides have been attached to mesoheme through an amide linkage between the heme propionate and the Lys N-ε nitrogen (Figure 4b). 42 Investigation of this peptide sandwiched mesoporphyrin system showed that His to heme ligation is mainly responsible for the peptide transformation from random coil to helix. Independently, the same propionate-Lys linkage strategy has been exploited to attach deuteroporphyrin to peptides whose sequence is derived from the F helix of hemoglobin β-chain.…”

Section: Metalloprotein Design and Engineeringmentioning

confidence: 99%

Metalloprotein Design & Engineering

2005

Encyclopedia of Inorganic Chemistry

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This review covers recent advances in metalloprotein design, with focus on different approaches to the design. Impressive progress has been made in designing metal‐binding sites in peptides, de novo designed proteins, and native protein scaffolds. The approach can be rational or combinatorial. Under rational design, redesigning an existing metal‐binding site to a new site with dramatically different structure and function complements well the design of new metal‐binding sites by revealing the role of specific residues responsible for a particular structural or functional feature of the metal‐binding site of interest. To create a new metal‐binding site, several approaches have been used, including design based on structural homology, by inspection, using automated computer search algorithms, or combination of the above approaches. In addition, modular approach by transplanting a conserved structural unit from one protein into another has also been shown to be effective. Design through combinatorial and evolution methods has also been successful as it requires little prior knowledge of the protein structure. Finally, introducing unnatural amino acids or nonnative metal ions/prosthetic groups to expand the repertoires of metalloproteins have been demonstrated. Successful examples of each of the approaches are given; advantages and disadvantages of the approaches are discussed; the outlook for future research is also presented.

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Design, Synthesis, and Circular Dichroism Investigation of a Peptide-Sandwiched Mesoheme

Cited by 103 publications

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EPR study of a novel [Fe–porphyrin] catalyst

EPR study of a novel [Fe–porphyrin] catalyst

Structural propensities in the heme binding region of apocytochrome b₅. II. Heme conjugates

Metalloprotein Design & Engineering

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Design, Synthesis, and Circular Dichroism Investigation of a Peptide-Sandwiched Mesoheme

Cited by 103 publications

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EPR study of a novel [Fe–porphyrin] catalyst

EPR study of a novel [Fe–porphyrin] catalyst

Structural propensities in the heme binding region of apocytochrome b5. II. Heme conjugates

Metalloprotein Design & Engineering

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Structural propensities in the heme binding region of apocytochrome b₅. II. Heme conjugates