Publication:
Molecular Modeling of the Human Hemoglobin-Haptoglobin Complex Sheds Light on the Protective Mechanisms of Haptoglobin

dc.contributor.authorChanin Nantasenamaten_US
dc.contributor.authorVirapong Prachayasittikulen_US
dc.contributor.authorLeif Bulowen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherLunds Universiteten_US
dc.date.accessioned2018-10-19T04:30:51Z
dc.date.available2018-10-19T04:30:51Z
dc.date.issued2013-04-26en_US
dc.description.abstractHemoglobin (Hb) plays a critical role in human physiological function by transporting O2. Hb is safe and inert within the confinement of the red blood cell but becomes reactive and toxic upon hemolysis. Haptoglobin (Hp) is an acute-phase serum protein that scavenges Hb and the resulting Hb-Hp complex is subjected to CD163-mediated endocytosis by macrophages. The interaction between Hb and Hp is extraordinarily strong and largely irreversible. As the structural details of the human Hb-Hp complex are not yet available, this study reports for the first time on insights of the binding modalities and molecular details of the human Hb-Hp interaction by means of protein-protein docking. Furthermore, residues that are pertinent for complex formation were identified by computational alanine scanning mutagenesis. Results revealed that the surface of the binding interface of Hb-Hp is not flat and protrudes into each binding partner. It was also observed that the secondary structures at the Hb-Hp interface are oriented as coils and α-helices. When dissecting the interface in more detail, it is obvious that several tyrosine residues of Hb, particularly β145Tyr, α42Tyr and α140Tyr, are buried in the complex and protected from further oxidative reactions. Such finding opens up new avenues for the design of Hp mimics which may be used as alternative clinical Hb scavengers. © 2013 Nantasenamat et al.en_US
dc.identifier.citationPLoS ONE. Vol.8, No.4 (2013)en_US
dc.identifier.doi10.1371/journal.pone.0062996en_US
dc.identifier.issn19326203en_US
dc.identifier.other2-s2.0-84876881709en_US
dc.identifier.urihttps://repository.li.mahidol.ac.th/handle/20.500.14594/31033
dc.rightsMahidol Universityen_US
dc.rights.holderSCOPUSen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84876881709&origin=inwarden_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleMolecular Modeling of the Human Hemoglobin-Haptoglobin Complex Sheds Light on the Protective Mechanisms of Haptoglobinen_US
dc.typeArticleen_US
dspace.entity.typePublication
mu.datasource.scopushttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84876881709&origin=inwarden_US

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