Edmundson A B, Ely K R
Ciba Found Symp. 1986;119:107-29. doi: 10.1002/9780470513286.ch7.
Synthetic peptides with chemotactic or opioid activity were bound to crystals of a light chain dimer and their three-dimensional structures and modes of binding were determined by X-ray analysis. The chemotactic series consisted of di- and tripeptides initiated with N-formylmethionine or N-formylnorleucine residues. Opioid peptides included the enkephalins and casomorphins ranging in length from four to seven residues. The binding region of the protein proved to be malleable in adjusting to the surface contours of the peptides. Aromatic contact residues, as well as polypeptide segments of hypervariable loops, moved to improve the complementarity with the ligands. The peptides were even more flexible and tended to conform fairly closely to the space and geometry available for occupancy in the binding sites. Binding interactions were not confined to the interior of the cavity. In both the chemotactic and opioid series, the carboxyl tails of the peptides encroached upon the outer surfaces of the rim and contributed to the binding energies for the protein-ligand complexes. The peptide bond in N-formylmethionyltryptophan was found to be in the energetically unfavourable cis configuration. There was also evidence for less severe distortions in peptide bond geometry when N-formyltripeptides were bound to the dimer.
具有趋化或阿片样活性的合成肽与轻链二聚体晶体结合，并通过X射线分析确定其三维结构和结合模式。趋化系列由以N-甲酰甲硫氨酸或N-甲酰正亮氨酸残基起始的二肽和三肽组成。阿片样肽包括长度为四至七个残基的脑啡肽和酪蛋白吗啡。事实证明，该蛋白质的结合区域在适应肽的表面轮廓方面具有可塑性。芳香族接触残基以及高变环的多肽片段会移动，以改善与配体的互补性。肽更加灵活，并且倾向于与结合位点中可占据的空间和几何形状相当紧密地契合。结合相互作用并不局限于腔的内部。在趋化和阿片样系列中，肽的羧基末端都侵入边缘的外表面，并对蛋白质-配体复合物的结合能有贡献。发现N-甲酰甲硫氨酰色氨酸中的肽键处于能量不利的顺式构型。也有证据表明，当N-甲酰三肽与二聚体结合时，肽键几何结构的扭曲程度较轻。
