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Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains.

Publication ,  Journal Article
Bonaventura, C; Cashon, R; Bonaventura, J; Perutz, M; Fermi, G; Shih, DT
Published in: The Journal of biological chemistry
December 1991

Hemoglobin (Hb) Chico (Lys beta 66----Thr at E10) has a diminished oxygen affinity (Shih, D. T.-b., Jones, R. T., Shih, M. F.-C., Jones, M. B., Koler, R. D., and Howard, J. (1987) Hemoglobin 11, 453-464). Our studies show that its P50 is about twice that of Hb A and that its cooperativity, anion, and Bohr effects between pH 7 and 8 are normal. The Bohr effect above pH 8 is somewhat reduced, indicating a small but previously undocumented involvement of the ionic bond formed by Lys beta 66 in the alkaline Bohr effect. Since the oxygen affinity of the alpha-hemes is likely to be normal, that of the beta-hemes in the tetramer is likely to be reduced by the equivalent of 1.2 kcal/mol beta-heme in binding energy. Remarkably, both initial and final stages of oxygen binding to Hb Chico are of lowered affinity relative to Hb A under all conditions examined. The isolated beta chains also show diminished oxygen affinity. In T-state Hb A, Lys(E10 beta) forms a salt bridge with one of the heme propionates, but comparison with other hemoglobin variants shows that rupture of this bridge cannot be the cause of the low oxygen affinity. X-ray analysis of the deoxy structure has now shown that Thr beta 66 either donates a hydrogen bond to or accepts one from His beta 63 via a bridging water molecule. This introduces additional steric hindrance to ligand binding to the T-state that results in slower rates of ligand binding. We measured the O2/CO partition coefficient and the kinetics of oxygen dissociation and carbon monoxide binding and found that lowered O2 and CO affinity is also exhibited by the R-state tetramers and the isolated beta chains of Hb Chico.

Duke Scholars

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

December 1991

Volume

266

Issue

34

Start / End Page

23033 / 23040

Related Subject Headings

  • X-Ray Diffraction
  • Oxygen
  • Models, Molecular
  • Ligands
  • Kinetics
  • Hydrogen-Ion Concentration
  • Humans
  • Histidine
  • Hemoglobins, Abnormal
  • Carbon Monoxide
 

Citation

APA
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ICMJE
MLA
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Bonaventura, C., Cashon, R., Bonaventura, J., Perutz, M., Fermi, G., & Shih, D. T. (1991). Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains. The Journal of Biological Chemistry, 266(34), 23033–23040. https://doi.org/10.1016/s0021-9258(18)54459-8
Bonaventura, C., R. Cashon, J. Bonaventura, M. Perutz, G. Fermi, and D. T. Shih. “Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains.The Journal of Biological Chemistry 266, no. 34 (December 1991): 23033–40. https://doi.org/10.1016/s0021-9258(18)54459-8.
Bonaventura C, Cashon R, Bonaventura J, Perutz M, Fermi G, Shih DT. Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains. The Journal of biological chemistry. 1991 Dec;266(34):23033–40.
Bonaventura, C., et al. “Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains.The Journal of Biological Chemistry, vol. 266, no. 34, Dec. 1991, pp. 23033–40. Epmc, doi:10.1016/s0021-9258(18)54459-8.
Bonaventura C, Cashon R, Bonaventura J, Perutz M, Fermi G, Shih DT. Involvement of the distal histidine in the low affinity exhibited by Hb Chico (Lys beta 66----Thr) and its isolated beta chains. The Journal of biological chemistry. 1991 Dec;266(34):23033–23040.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

December 1991

Volume

266

Issue

34

Start / End Page

23033 / 23040

Related Subject Headings

  • X-Ray Diffraction
  • Oxygen
  • Models, Molecular
  • Ligands
  • Kinetics
  • Hydrogen-Ion Concentration
  • Humans
  • Histidine
  • Hemoglobins, Abnormal
  • Carbon Monoxide