title: The role of amino acid alpha38 in the control of oxygen binding to human adult and embryonic haemoglobin Portland.
abstract: The role of the amino acid at position alpha(38) in haemoglobin has been probed using site-directed mutagenesis. When the Thr residue at position alpha(38) (which is totally conserved in all mammals) is changed to a Gln, the equilibrium properties of the protein are significantly altered. Equilibrium and kinetic data show that the R-state properties of the protein are essentially unaffected by the mutation whilst the allosteric equilibrium and T-state properties are changed. Mutation of the naturally occurring Gln(38) of the human embryonic haemoglobin zeta-chain (the only known non-Thr containing globin) to a Thr residue shows the converse change in properties produced by the adult mutation, although in this case the situation is complicated by significant chain heterogeneity in the T state. An extension of the two-state model of co-operativity is presented to describe quantitatively the equilibrium ligand binding in the presence of T-state chain heterogeneity. A molecular model is described in which the putative interaction of alphaGln(38) and betaTyr(145) is identified which make a significant contribution to the previously reported unusual ligand-binding properties of the zeta-chain containing human embryonic haemoglobins.
authors.affiliation: Biochemistry and Molecular Biology, School of Biological Sciences, University of Auckland, New Zealand.
authors.forename: T
authors.initials: T
authors.lastname: Zheng
authors.forename: T
authors.initials: T
authors.lastname: Brittain
authors.forename: N J
authors.initials: NJ
authors.lastname: Watmough
authors.forename: R E
authors.initials: RE
authors.lastname: Weber
mesh_terms: D000328:Adult; D001665:Binding Sites; D005319:Fetal Hemoglobin / Q000737:chemistry / Q000378:metabolism*; D006441:Hemoglobin A / Q000737:chemistry / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D006455:Hemoglobins, Abnormal; D010108:Oxyhemoglobins; D011994:Recombinant Proteins; C030447:hemoglobin Portland; D006441:Hemoglobin A; D005319:Fetal Hemoglobin; D010100:Oxygen