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Role of the Chemical Environment beyond the Coordination Site: Structural Insight into Fe III Protoporphyrin Binding to Cysteine‐Based Heme‐Regulatory Protein Motifs
Author(s) -
Brewitz Hans Henning,
Kühl Toni,
Goradia Nishit,
Galler Kerstin,
Popp Jürgen,
Neugebauer Ute,
Ohlenschläger Oliver,
Imhof Diana
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500331
Subject(s) - heme , chemistry , cysteine , hemeprotein , protoporphyrin ix , protein structure , peptide , amino acid , binding site , stereochemistry , biochemistry , enzyme , organic chemistry , photodynamic therapy
The importance of heme as a transient regulatory molecule has become a major focus in biochemical research. However, detailed information about the molecular basis of transient heme–protein interactions is still missing. We report an in‐depth structural analysis of Fe III heme–peptide complexes by a combination of UV/Vis, resonance Raman, and 2D‐NMR spectroscopic methods. The experiments reveal insights both into the coordination to the central iron ion and into the spatial arrangement of the amino acid sequences interacting with protoporphyrin IX. Cysteine‐based peptides display different heme‐binding behavior as a result of the existence of ordered, partially ordered, and disordered conformations in the heme‐unbound state. Thus, the heme‐binding mode is clearly the consequence of the nature and flexibility of the residues surrounding the iron ion coordinating cysteine. Our analysis reveals scenarios for transient binding of heme to heme‐regulatory motifs in proteins and demonstrates that a thorough structural analysis is required to unravel how heme alters the structure and function of a particular protein.