title: Role of the Chemical Environment beyond the Coordination Site: Structural Insight into Fe(III) Protoporphyrin Binding to Cysteine-Based Heme-Regulatory Protein Motifs.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn, Brühler Strasse 7, 53119, Bonn, Germany.
authors.forename: Hans Henning
authors.initials: HH
authors.lastname: Brewitz
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Laboratoire BIP-UMR 7281, 31, chemin Joseph Aiguier, Batiment IM, 13009, Marseille, France.
authors.forename: Toni
authors.initials: T
authors.lastname: Kühl
authors.affiliation: Biomolecular NMR Spectroscopy, Leibniz Institute for Age Research-Fritz Lipmann Institute, Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Nishit
authors.initials: N
authors.lastname: Goradia
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.|Leibniz Institute of Photonic Technology, Albert-Einstein-Strasse 9, 07745, Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Galler
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.|Leibniz Institute of Photonic Technology, Albert-Einstein-Strasse 9, 07745, Jena, Germany.|Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743, Jena, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Popp
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747, Jena, Germany.|Leibniz Institute of Photonic Technology, Albert-Einstein-Strasse 9, 07745, Jena, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Neugebauer
authors.affiliation: Biomolecular NMR Spectroscopy, Leibniz Institute for Age Research-Fritz Lipmann Institute, Beutenbergstrasse 11, 07745, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ohlenschläger
authors.affiliation: Department of Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn, Brühler Strasse 7, 53119, Bonn, Germany. dimhof@uni-bonn.de.
authors.forename: Diana
authors.initials: D
authors.lastname: Imhof
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism*; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D006420:Hemeproteins; D011524:Protoporphyrins; C028025:protoporphyrin IX; D003545:Cysteine
keywords: heme regulatory motifs; heme-binding proteins; heme-peptide complexes; protein structures; spectroscopic methods