Probing the energetics of proteins through structural perturbation: sites of regulatory energy in human hemoglobin.
Probing the energetics of proteins through structural perturbation: sites of regulatory energy in human hemoglobin.
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DOI：
10.1073/pnas.79.6.1849
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发表时间：
1982-03
影响因子：
11.1
通讯作者：
D. W. Pettigrew;P. Romeo;A. Tsapis;J. Thillet;M. L. Smith;B. W. Turner;G. K. Ackers
中科院分区：
文献类型：
--
作者：
D. W. Pettigrew;P. Romeo;A. Tsapis;J. Thillet;M. L. Smith;B. W. Turner;G. K. Ackers
通过对单个氨基酸残基结构改变的分子能量响应的广泛研究，确定了人血红蛋白分子内调节氧亲和力的能量转导位点。对于22个突变和化学修饰的血红蛋白，我们确定了四聚体分子在四个结合步骤中改变氧亲和力所使用的总自由能。结果表明，氧结合亲和力的调节是由于能量的变化，而能量的变化主要集中在α 1 β 2界面。它们还表明在这个接触区域内存在高度的“内部合作”。，单个残基位置的结构扰动是能量耦合的。因此，配体结合中的协同性反映了更深层次的协同性——α 1 β 2界面域内蛋白质-蛋白质相互作用的协同性。
The sites of energy transduction within the human hemoglobin molecule for the regulation of oxygen affinity have been determined by an extensive study of the molecule's energetic response to structural alteration at individual amino acid residues. For 22 mutant and chemically modified hemoglobins we have determined the total free energy used by the tetrameric molecule for alteration of oxygen affinity at the four binding steps. The results imply that the regulation of oxygen binding affinity is due to energy changes which are mostly localized at the alpha 1 beta 2 interface. They also indicate a high degree of "internal cooperativity" within this contact region--i.e., the structural perturbations at individual residue sites are energetically coupled. Cooperativity in ligand binding is thus a reflection of cooperativity at a deeper level--that of the protein-protein interactions within the alpha 1 beta 2 interfacial domain.