1bzz

File:1bzz.gif

spinqualitylabelsall models 1bzz, resolution 1.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HEMOGLOBIN (ALPHA V1M) MUTANT

OverviewOverview

Human hemoglobin produced in the Escherichia coli coexpression system of, Hernan et al. [(1992) Biochemistry 31, 8619-8628] has been transformed, into a functionally homogeneous protein whose properties closely, approximate those of normal hemoglobin A. Both of the alpha and beta, chains of this hemoglobin contain a valine-methionine substitution at, position 1 in order to accommodate the difference in specificity of the, protein-processing enzymes of procaryotes. Despite extensive purification, functional homogeneity of the E. coli expressed hemoglobin was achieved, only by the complete disassembly of the hemoglobin into its component, alpha and beta globins and their reassembly in the presence of hemin. The, kinetics of CO combination and the thermodynamics of O2 binding and, cooperativity of the reassembled alphaV1M-betaV1M hemoglobin closely, approximate those of HbA. The alpha globin obtained from the E. coli, expressed hemoglobin was also combined with normal human beta chains and, hemin to form the alphaV1M variant. The alpha+M variant of HbA, in which, the normal N-terminal valine of the alpha chains is preceded by a, methionine residue, was prepared by the same procedure. The kinetics of, the reactions of CO with the alphaV1M and alpha+M variants are similar to, those for HbA. The equilibria of oxygen binding to alphaV1M and HbA are, similar whereas alpha+M exhibits a significantly higher oxygen affinity., The three-dimensional structures of alphaV1M and alpha+M offer an, explanation for the latter affinity difference. Although the structures of, alphaV1M and HbA, which have been determined by X-ray crystallography, are, virtually indistinguishable except at the N-terminal residues, that of, alpha+M indicates the displacement of a solvent molecule, possibly a, chloride ion, from arginine 141alpha. Such an alteration in an anion, binding site could result in increased oxygen affinity.

DiseaseDisease

Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], Erythrocytosis OMIM:[141850], HPFH, deletion type OMIM:[141900], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Heinz body anemias, beta- OMIM:[141900], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia, alpha- OMIM:[141850], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, alpha- OMIM:[141800], Thalassemias, beta- OMIM:[141900]

About this StructureAbout this Structure

1BZZ is a Protein complex structure of sequences from Homo sapiens with HEM as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Structural and functional properties of human hemoglobins reassembled after synthesis in Escherichia coli., Hui HL, Kavanaugh JS, Doyle ML, Wierzba A, Rogers PH, Arnone A, Holt JM, Ackers GK, Noble RW, Biochemistry. 1999 Jan 19;38(3):1040-9. PMID:9894000

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