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2,3-DPG-Hb complex: a hypothesis for an asymmetric binding.

机译:2,3-DPG-Hb复合物:不对称结合的假设。

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摘要

This study was undertaken to test the symmetry of 2,3-diphosphoglycerate (2,3-DPG) binding site in hemoglobin (Hb). From Arnone's study [A. Arnone, Nature (London) 237 (1972) 146] the 2,3-DPG binding site is located at the top of the cavity, that runs through the center of the deoxy-Hb molecule. However, it is possible that this symmetry reported by Arnone, for crystals of 2,3-DPG-Hb complex, might not be conserved in solution. In this paper, we report the 31P nuclear magnetic resonances of the 2,3-DPG interaction with Hb. The 2,3-DPG chemical shifts of the P2 and P3 resonance are both pH- and hemoglobin-dependent [protein from man, polar bear (Ursus maritimus), Arctic fox (Alopex lagopus) and bovine]. 2,3-DPG binds tightly to deoxyhemoglobin and weakly, nevertheless significantly, to oxyhemoglobin. In particular, our results suggest similar spatial position of the binding site of 2,3-DPG in both forms of Hb in solutions. However, the most unexpected result was the apparent loss of symmetry in the binding site, which might correlate with the ability of the hemoglobin to modulate its functional behavior. The different interactions of the phosphate groups indicate small differences in the quaternary structure of the different deoxy forms of hemoglobin. Given the above structural perturbation an asymmetric binding in the complex could justify, at least in part, different physiological properties of Hb. Regardless, functionally relevant effects of 2,3-DPG seem to be measured and best elucidated through solution studies.
机译:进行这项研究以测试血红蛋白(Hb)中2,3-二磷酸甘油酸酯(2,3-DPG)结合位点的对称性。摘自Arnone的研究[A. [Arnone,Nature(London)237(1972)146]中,2,3-DPG结合位点位于腔的顶部,穿过脱氧Hb分子的中心。然而,对于溶液中的2,3-DPG-Hb配合物晶体,Arnone报告的这种对称性可能是不守恒的。在本文中,我们报告了2,3-DPG与Hb相互作用的31P核磁共振。 P2和P3共振的2,3-DPG化学位移均依赖于pH和血红蛋白[来自人,北极熊(Ursus maritimus),北极狐狸(Alopex lagopus)和牛的蛋白质]。 2,3-DPG与脱氧血红蛋白紧密结合,但与氧合血红蛋白弱结合,但显着结合。特别地,我们的结果表明溶液中两种形式的Hb中2,3-DPG结合位点的空间位置相似。然而,最出乎意料的结果是结合位点的对称性明显丧失,这可能与血红蛋白调节其功能行为的能力有关。磷酸基团的不同相互作用表明,不同脱氧形式的血红蛋白的四级结构存在细微差异。考虑到以上结构扰动,复合物中的不对称结合可以至少部分地证明Hb的不同生理特性是合理的。无论如何,似乎已通过解决方案研究对2,3-DPG的功能相关作用进行了测量和阐明。

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