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PLoS One 2013;8(3):e59841

Haptoglobin Preferentially Binds beta but Not alpha Subunits Cross-Linked Hemoglobin Tetramers with Minimal Effects on Ligand and Redox Reactions.

Jia Y, Wood F, Buehler PW, Alayash AI

Abstract

Human hemoglobin (Hb) and haptoglobin (Hp) exhibit an extremely high affinity for each other, and the dissociation of Hb tetramers into dimers is generally believed to be a prerequisite for complex formation. We have investigated Hp interactions with native Hb, aa, and ßß cross-linked Hb (aaXLHb and ßßXLHb, respectively), and rapid kinetics of Hb ligand binding as well as the redox reactivity in the presence of and absence of Hp. The quaternary conformation of ßß subunit cross-linking results in a higher binding affinity than that of aa subunit cross-linked Hb. However, ßß cross-linked Hb exhibits a four fold slower association rate constant than the reaction rate of unmodified Hb with Hp. The Hp contact regions in the Hb dimer interfaces appear to be more readily exposed in ßßXLHb than aaXLHb. In addition, apart from the functional changes caused by chemical modifications, Hp binding does not induce appreciable effects on the ligand binding and redox reactions of ßßXLHb. Our findings may therefore be relevant to the design of safer Hb-based oxygen therapeutics by utilizing this preferential binding of ßßXLHb to Hp. This may ultimately provide a safe oxidative inactivation and clearance pathway for chemically modified Hbs in circulation.


Category: Journal Article
PubMed ID: #23555800 DOI: 10.1371/journal.pone.0059841
PubMed Central ID: #PMC3612097
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2012-11-02 Entry Last Modified: 2014-01-08
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