Inhibitory effect of deoxyhemoglobin A2 on the rate of deoxyhemoglobin S polymerization. |
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Authors: | M R Waterman G L Cottam K Shibata |
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Institution: | Department of Biochemistry The University of Texas Health Science Center at Dallas Dallas, TX 75235, U.S.A. |
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Abstract: | From a consideration of the primary sequence of hemoglobin A2 and the reported 5 å molecular contacts between deoxyhemoglobin S molecules in a crystal, it is predicted that hemoglobin A2 might act as an inhibitor of the polymerization of deoxyhemoglobin S in a manner similar to hemoglobin. F. This has been tested experimentally by measuring the rate of change of the transverse water proton relaxation times (T2) in equimolar mixtures of hemoglobin S and one of the non-gelling hemoglobins A, F or A2. Hemoglobins A2 and F have far more pronounced inhibitory effects on the rate of polymerization than does hemoglobin A. These molecules contain several amino acid differences from hemoglobin A beta chains which are located in the 5 Å molecular crystal contacts and these altered crystal contacts result in a much stronger inhibition of the rate of polymerization. Since hemoglobin A2 is a normal hemoglobin found in small amounts in all adult red cells, increased delta chain synthesis may have potential importance in therapy for sickle cell disease. |
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