Chen Y W, Fersht A R
Centre for Protein Engineering, Medical Research Council Centre, Cambridge, UK.
FEBS Lett. 1994 Jun 27;347(2-3):304-9. doi: 10.1016/0014-5793(94)00574-5.
The solvation of polar groups at the N-terminal end of alpha-helices was studied by comparing the crystal structures of T4 lysozyme, barley chymotrypsin inhibitor 2 (CI2), barnase and their respective N-cap mutants. Whether or not the N3 residue is solvated on mutating the N-cap Thr/Ser to Ala or Gly appears to be related to the identities and the side-chain conformations of the N2 and N3 residues. When these two residues are alanines, as is in the pseudo-wild-type CI2 (E33A/E34A), the main-chain NH at the N3 position is exposed to the solvent and can be solvated. If the N2 residue is an Asp or a Glu, it is more likely that the side-chain of these residues will form a surrogate N-cap with the amide NH at N3 to compensate for the lost -OH group. In this case, no additional solvation will be observed. In general, Gly can be more stable than Ala at the N-cap because its small side-chain allows nearby polar groups to form hydrogen bonds with optimal geometry with solvent molecules or other polar groups.
通过比较T4溶菌酶、大麦胰凝乳蛋白酶抑制剂2（CI2）、芽孢杆菌RNA酶及其各自的N-帽突变体的晶体结构，研究了α-螺旋N端极性基团的溶剂化情况。将N-帽苏氨酸/丝氨酸突变为丙氨酸或甘氨酸时，N3残基是否被溶剂化似乎与N2和N3残基的特性及侧链构象有关。当这两个残基为丙氨酸时，如在假野生型CI2（E33A/E34A）中，N3位置的主链NH暴露于溶剂中并可被溶剂化。如果N2残基为天冬氨酸或谷氨酸，则这些残基的侧链更有可能与N3处的酰胺NH形成替代N-帽，以补偿失去的-OH基团。在这种情况下，不会观察到额外的溶剂化现象。一般来说，甘氨酸在N-帽处可能比丙氨酸更稳定，因为其小侧链允许附近的极性基团与溶剂分子或其他极性基团以最佳几何形状形成氢键。
