De novo design of DeltaF -containing heme-binding peptides

The structural characterization of de novo designed metalloproteins together with determination of chemical reactivity can provide a detailed understanding of the relationship between protein structure and functional properties. Toward this goal, using the basic scaffold of 1pbz (Rosenblatt et al. (...

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Bibliographic Details
Published in:Chemical biology & drug design 2007-02, Vol.69 (2), p.119-123
Main Authors: Rai, Jagdish, Raghothama, S, Sahal, D
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Cobalt - chemistry
Coproporphyrins - chemistry
Heme - chemistry
Histidine - chemistry
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Peptides, Cyclic - chemistry
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Summary:The structural characterization of de novo designed metalloproteins together with determination of chemical reactivity can provide a detailed understanding of the relationship between protein structure and functional properties. Toward this goal, using the basic scaffold of 1pbz (Rosenblatt et al. (2003) Proc Natl Acad Sci U S A;100:13140) we have designed cyclic DeltaF-containing heme-binding peptides. The alpha- and beta-bands in UV-Vis spectroscopy are indicative of bis-His-ligated heme complex. Most of our DeltaF-containing peptides have more affinity to cobalt(III)Coproporphyrinate-I than heme because cobalt(III)Coproporphyrinate-I contains two additional propionate groups which can have salt bridge interactions with the lysine residues in the peptide. Helicity induction in peptide by DeltaF and aromatic interaction of DeltaF with heme have increased the heme affinity of CP-6-12pbz (cyclic peptide with substitutions of Ala at positions 6 and 12 by DeltaF; 905/mm) compared with 1pbz (279/mm). The nuclear magnetic resonance spectra are indicative of overall helical structure for CP-6-12pbz and CP-6-12pbz in complex with cobalt (III)Coproporphyrinate-I. The descending order of heme affinity in peptides (CP-6-12pbz > CP-12pbz > CP-5-12pbz) indicates that DeltaF at i + 3 or i - 3 from the central H9 favors heme binding but disrupts the same when placed at i - 4.
ISSN:1747-0277