Author:
Hopp Marie-T.,Paul George Ajay A.,Ramoji Anuradha,Pepanian Anna,Detzel Milena S.,Neugebauer Ute,Imhof Diana
Abstract
AbstractUnder hemolytic conditions, toxic heme is scavenged by hemopexin. Recently, the heme-binding properties of hemopexin have been reassessed, which revealed a KD of ~ 0.32 nM as well as a stoichiometry of one to two heme molecules binding to hemopexin. A 66mer hemopexin-derived peptide that spans over three heme-binding motifs was used to verify the earlier suggested heme-recruiting mechanism. Herein, we employed spectroscopic and computational methods to substantiate the hypothesis of more than one heme molecule binding to hemopexin and to analyze the heme-binding mode. Both, hemopexin and the 66mer peptide, were found to bind heme in mixed penta- and hexacoordinated states, which strongly indicates that heme binding follows distinct criteria and increases rigidity of the peptide-heme complex. Additional in silico molecular dynamics simulations support these experimental findings and, thus, contribute to our understanding of the molecular basis of the heme-hemopexin interaction. This analysis provides further details for consideration of hemopexin in biomedical applications.
Funder
Rheinische Friedrich-Wilhelms-Universität Bonn
Publisher
Springer Science and Business Media LLC
Subject
Drug Discovery,Molecular Medicine,Biochemistry,Bioengineering,Analytical Chemistry
Cited by
2 articles.
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