Structure and function of hemoglobin variants at an internal hydrophobic site: Consequences of mutations at the. beta. 27 (B9) position

Journal Article · Tue Jul 31 04:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00482a010· OSTI ID:5985984

Huang, Yue; Pagnier, J; Magne, P; Kister, J; Poyart, C ^[1]; Baklouti, F; Delaunay, J ^[2]; Fermi, G; Perutz, M F ^[3]

---

1. Institut National de la Sante et de la Recherche Medicale, Le Kremlin-Bicetre (France)
2. Centre National de la Recherche Scientifique, Lyon (France)
3. MRC Laboratory for Molecular Biology, Cambridge (England)

The authors have studied the structure-function relationships in newly discovered hemoglobin (Hb) mutants with substitutions occurring at the tight and highly hydrophobic cluster between the B and G helices in the {beta} chains, namely, Hb Knossos or {beta} A27S and Hb Grange-Blanche or {beta} A27V. The {beta} A27S mutant has a 50% decrease in oxygen affinity relative to native human Hb A, while the {beta} A27V mutant has an increased oxygen affinity. They have also engineered the artificial {beta} A27T mutation through site-directed mutagenesis. This new mutant exhibits functional properties similar to those of Hb A. None of these mutants is unstable. X-ray analyses show that the substitution of Val for Ala may reduce the relative stability of the T structure of the molecule through packing effects in the {beta} chains; for the {beta} A27S mutant a new hydrogen bond between serine and the carbonyl O at {beta} 23 (B5) Val is observed and is likely to increase the relative stability of the T structure in the mutant hemoglobin. However, no significant changes in the crystals were observed for these mutants between the quaternary R and T structures relative to native Hb A. They conclude that small tertiary structural changes in the tight hydrophobic B-G helix interface are sufficient to induce functional abnormalities resulting in either low or high intrinsic oxygen affinities.

• OSTI ID: 5985984
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:30; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550602* -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ATOMIC MODELS
CARBOXYLIC ACIDS
COHERENT SCATTERING
DIFFRACTION
ELECTRON DENSITY
ELEMENTS
GLOBINS
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MATHEMATICAL MODELS
MUTANTS
NONMETALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN
PIGMENTS
PORPHYRINS
PROTEINS
SCATTERING
STRUCTURE-ACTIVITY RELATIONSHIPS
VALINE
X-RAY DIFFRACTION