1bab

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Template:STRUCTURE 1bab

HEMOGLOBIN THIONVILLE: AN ALPHA-CHAIN VARIANT WITH A SUBSTITUTION OF A GLUTAMATE FOR VALINE AT NA-1 AND HAVING AN ACETYLATED METHIONINE NH2 TERMINUS


Overview

In hemoglobin (Hb) Thionville, the substitution of a glutamic acid for the alpha-chain NH2-terminal valine inhibits the cleavage of the initiator methionine which is then acetylated. The elongation of the alpha-chain NH2 terminus modifies the three-dimensional structure of hemoglobin at a region that is known to have an important role in the allosteric regulation of oxygen binding. Relative to Hb A, Hb Thionville has a lower affinity for oxygen, and the heterotropic allosteric effects of protons, chloride, and bezafibrate are reduced. In contrast, the response to 2,3-diphosphoglycerate is normal. Analysis of oxygen equilibrium data within the framework of the two-state allosteric model indicates that the structure of deoxy Hb Thionville is stabilized relative to that of deoxy Hb A. The x-ray crystal structure of deoxy Hb Thionville shows that the glutamate side chain extends away from the alpha 1-alpha 2 interface, whereas the methionine side chain (which has two conformations) extends into the alpha 1-alpha 2 interface, physically displacing chloride and bezafibrate. The increased stability of deoxy Hb Thionville is due to new intrasubunit and intersubunit contacts made by the methionine. These interactions replace the indirect contacts, made through bound chloride ions, that Val-1 alpha normally contributes to the alpha 1-alpha 2 interface.

About this Structure

1BAB is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Hemoglobin Thionville. An alpha-chain variant with a substitution of a glutamate for valine at NA-1 and having an acetylated methionine NH2 terminus., Vasseur C, Blouquit Y, Kister J, Prome D, Kavanaugh JS, Rogers PH, Guillemin C, Arnone A, Galacteros F, Poyart C, et al., J Biol Chem. 1992 Jun 25;267(18):12682-91. PMID:1618774 Page seeded by OCA on Fri May 2 11:16:25 2008

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