Altered ligand rebinding kinetics due to distal-side effects in hemoglobin Chico (Lys(β66) (E10) → Thr)

Celia Bonaventurat, Joseph Bonaventura, Daniel Tzu Bi Shih, E. Timothy Iben, Joel M. Friedman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Hb Chico is an unusual human hemoglobin variant that has lowered oxygen affinity, but unaltered cooperativity and anion sensitivity. Previous studies showed these features to be associated with distal-side heme pocket alterations that confer increased structural rigidity on the molecule and that increase water content in the β-chain heme pocket. We report here that the extent of nanosecond geminate rebinding of oxygen to the variant and its isolated β-chains is appreciably decreased. Structural alterations in this variant decrease its oxygen recombination rates without significantly altering rates of migration out of the heme pocket. Data analysis indicates that one or more barriers that impede rebinding of oxygen from docking sites in the heme pocket are increased, with less consequences for CO rebinding. Resonance Raman spectra show no significant alterations in spectral regions sensitive to interactions between the heme iron and the proximal histidine residue, confirming that the functional differences in the variant are due to distal-side heme pocket alterations. These effects are discussed in the context of a schematic representation of heme pocket wells and barriers that could aid the design of novel hemoglobins with altered ligand affinity without loss of the normal allosteric responses that facilitate unloading of oxygen to respiring tissues.

Original languageEnglish (US)
Pages (from-to)8686-8693
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number13
DOIs
StatePublished - Mar 26 1999

Fingerprint

Heme
Ligands
Kinetics
Oxygen
Hemoglobins
Schematic diagrams
Carbon Monoxide
hemoglobin Chico
Unloading
Histidine
Rigidity
Water content
Genetic Recombination
Anions
Raman scattering
Iron
Tissue
Molecules
Water

ASJC Scopus subject areas

  • Biochemistry

Cite this

Altered ligand rebinding kinetics due to distal-side effects in hemoglobin Chico (Lys(β66) (E10) → Thr). / Bonaventurat, Celia; Bonaventura, Joseph; Shih, Daniel Tzu Bi; Iben, E. Timothy; Friedman, Joel M.

In: Journal of Biological Chemistry, Vol. 274, No. 13, 26.03.1999, p. 8686-8693.

Research output: Contribution to journalArticle

Bonaventurat, Celia ; Bonaventura, Joseph ; Shih, Daniel Tzu Bi ; Iben, E. Timothy ; Friedman, Joel M. / Altered ligand rebinding kinetics due to distal-side effects in hemoglobin Chico (Lys(β66) (E10) → Thr). In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 13. pp. 8686-8693.
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