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Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking.

Publication ,  Journal Article
Strader, MB; Bangle, R; Parker Siburt, CJ; Varnado, CL; Soman, J; Benitez Cardenas, AS; Samuel, PP; Singleton, EW; Crumbliss, AL; Olson, JS ...
Published in: The Biochemical journal
December 2017

Previous work suggested that hemoglobin (Hb) tetramer formation slows autoxidation and hemin loss and that the naturally occurring mutant, Hb Providence (HbProv; βK82D), is much more resistant to degradation by H2O2 We have examined systematically the effects of genetic cross-linking of Hb tetramers with and without the HbProv mutation on autoxidation, hemin loss, and reactions with H2O2, using native HbA and various wild-type recombinant Hbs as controls. Genetically cross-linked Hb Presbyterian (βN108K) was also examined as an example of a low oxygen affinity tetramer. Our conclusions are: (a) at low concentrations, all the cross-linked tetramers show smaller rates of autoxidation and hemin loss than HbA, which can dissociate into much less stable dimers and (b) the HbProv βK82D mutation confers more resistance to degradation by H2O2, by markedly inhibiting oxidation of the β93 cysteine side chain, particularly in cross-linked tetramers and even in the presence of the destabilizing Hb Presbyterian mutation. These results show that cross-linking and the βK82D mutation do enhance the resistance of Hb to oxidative degradation, a critical element in the design of a safe and effective oxygen therapeutic.

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Published In

The Biochemical journal

DOI

EISSN

1470-8728

ISSN

0264-6021

Publication Date

December 2017

Volume

474

Issue

24

Start / End Page

4171 / 4192

Related Subject Headings

  • Protein Engineering
  • Oxidation-Reduction
  • Mutation, Missense
  • Hydrogen Peroxide
  • Humans
  • Hemoglobins
  • Dimerization
  • Cross-Linking Reagents
  • Biochemistry & Molecular Biology
  • 3101 Biochemistry and cell biology
 

Citation

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Strader, M. B., Bangle, R., Parker Siburt, C. J., Varnado, C. L., Soman, J., Benitez Cardenas, A. S., … Alayash, A. I. (2017). Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking. The Biochemical Journal, 474(24), 4171–4192. https://doi.org/10.1042/bcj20170491
Strader, Michael Brad, Rachel Bangle, Claire J. Parker Siburt, Cornelius L. Varnado, Jayashree Soman, Andres S. Benitez Cardenas, Premila P. Samuel, et al. “Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking.The Biochemical Journal 474, no. 24 (December 2017): 4171–92. https://doi.org/10.1042/bcj20170491.
Strader MB, Bangle R, Parker Siburt CJ, Varnado CL, Soman J, Benitez Cardenas AS, et al. Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking. The Biochemical journal. 2017 Dec;474(24):4171–92.
Strader, Michael Brad, et al. “Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking.The Biochemical Journal, vol. 474, no. 24, Dec. 2017, pp. 4171–92. Epmc, doi:10.1042/bcj20170491.
Strader MB, Bangle R, Parker Siburt CJ, Varnado CL, Soman J, Benitez Cardenas AS, Samuel PP, Singleton EW, Crumbliss AL, Olson JS, Alayash AI. Engineering oxidative stability in human hemoglobin based on the Hb providence (βK82D) mutation and genetic cross-linking. The Biochemical journal. 2017 Dec;474(24):4171–4192.

Published In

The Biochemical journal

DOI

EISSN

1470-8728

ISSN

0264-6021

Publication Date

December 2017

Volume

474

Issue

24

Start / End Page

4171 / 4192

Related Subject Headings

  • Protein Engineering
  • Oxidation-Reduction
  • Mutation, Missense
  • Hydrogen Peroxide
  • Humans
  • Hemoglobins
  • Dimerization
  • Cross-Linking Reagents
  • Biochemistry & Molecular Biology
  • 3101 Biochemistry and cell biology