Characterisation of low free-energy excited states of folded proteins
Characterisation of low free-energy excited states of folded proteins
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DOI：
10.1006/jmbi.1998.2265
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发表时间：
1998-12-18
影响因子：
5.6
通讯作者：
Williamson, MP
中科院分区：
文献类型：
--
作者：
Baxter, NJ;Hosszu, LLP;Williamson, MP
它表明，身份的残基访问激发构象状态，即低自由能相对于基态的蛋白质的ape可以从酰胺质子NMR化学位移温度依赖性显示显着的曲率。对于磷酸甘油酸激酶、鸡蛋清溶菌酶和BPTI的N-末端结构域，构象异质性来自许多独立的来源，包括：由于蛋白质的部分缺失而导致的结构不稳定性;通过二硫键异构化产生的次要构象异构体;与埋藏的水分子相关的替代氢键网络;涉及骨架酰胺和表面暴露的侧链氢键受体的替代氢键;以及环、二级结构元件的末端和链末端的破坏。在许多这些情况下，在这些位点的构象异质性先前已经通过X-射线和/或NMR研究鉴定，但是掩埋水分子的构象异质性迄今很少受到关注。这些多个独立的低自由能激发态各自涉及少量的残基，并且显示出在基态的2.5 kcal mol（-1）内。他们的关系与部分未折叠的形式，其特征在于使用酰胺质子交换研究进行了讨论。(C)北京：科学出版社.
It is demonstrated that the identity of residues accessing excited conformational states that ape of low free energy relative to the ground state in proteins can be obtained from amide proton NMR chemical shift temperature dependences displaying significant curvature. For the N-terminal domain of phosphoglycerate kinase, hen egg-white lysozyme and BPTI, conformational heterogeneity arises from a number of independent sources, including: structural instability resulting from deletion of part of the protein; a minor conformer generated through disulphide bond iso merisation; an alternative hydrogen bond network associated with buried water molecules; alternative hydrogen bonds involving backbone amides and surface-exposed side-chain hydrogen bond accepters; and the disruption of loops, ends of secondary structural elements and chain termini. in many of these cases, the conformational heterogeneity at these sites has previously been identified by X-ray and/or NMR studies, but conformational heterogeneity of buried water molecules has hitherto received little attention. These multiple independent low free-energy excited states each involve a small number of residues and are shown to be within 2.5 kcal mol(-1) of the ground state. Their relationship with the partially unfolded forms previously characterised using amide proton exchange studies is discussed. (C) 1998 Academic Press.