Effect of the beta 73 amino acid on the hydrophobicity, solubility, and the kinetics of polymerization of deoxyhemoglobin S.

Published

Journal Article

The role of Asp-beta 73 on the surface hydrophobicity and solubility of hemoglobin was studied using Hb A, Hb S, Hb C Harlem (alpha 2 beta 2Val-6,Asn-73), and Hb Korle Bu (alpha 2 beta 2Asn-73). The surface hydrophobicity of the oxy form of these hemoglobins increased in the order of Hb A, Hb Korle Bu, Hb S, and Hb C Harlem, coinciding with the change in solubility. The same is not true for deoxyhemoglobins. The solubilities of deoxy-Hb S and deoxy-Hb C Harlem were much lower than that expected from their surface hydrophobicity. Although the hydrophobicity of deoxy-Hb C Harlem is greater than that of deoxy-Hb S, the solubility of deoxy-Hb S is only one-third that of deoxy-Hb C Harlem. This deviation must be caused by the substitution of Asn for Asp at the beta 73 position and its inhibitory effect on hydrogen bonding in Hb S polymers. The kinetics of the polymerization of 1:1 mixtures of the deoxy form of S-C Harlem, A-C Harlem, Korle Bu-S, and Korle Bu-C Harlem were studied in comparison with that of deoxy-Hb S and deoxy-Hb C Harlem alone. All of these binary mixtures polymerized with a distinct delay time prior to polymerization. Based on the results of kinetic studies, the probability factors for nucleation of S-C Harlem, A-S, A-C Harlem, S-Korle Bu, and Korle Bu-C Harlem hybrid hemoglobins were calculated as 0.65, 0.5, 0.5, 0.15, and 0.17, respectively, in comparison with that of Hb S (1.0). The probability factor for Hb C Harlem alone was 0.3. These data suggest that the Asp-beta 73 is directly involved in nucleation during Hb S polymerization and that the beta 73 is always trans to the active Val-beta 6 in the formation of nuclei.

Full Text

Duke Authors

Cited Authors

  • Adachi, K; Kim, J; Kinney, TR; Asakura, T

Published Date

  • August 1987

Published In

Volume / Issue

  • 262 / 22

Start / End Page

  • 10470 - 10474

PubMed ID

  • 3611079

Pubmed Central ID

  • 3611079

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng