Very short peptides with stable folds: building on the interrelationship of Trp/Trp, Trp/cation, and Trp/backbone-amide interaction geometries.
Very short peptides with stable folds: building on the interrelationship of Trp/Trp, Trp/cation, and Trp/backbone-amide interaction geometries.
复制标题
DOI：
10.1002/prot.22240
复制
发表时间：
2009-05-01
影响因子：
2.9
通讯作者：
Andersen, Niels H.
中科院分区：
文献类型：
--
作者：
Eidenschink, Lisa;Kier, Brandon L.;Huggins, Kelly N. L.;Andersen, Niels H.
通过将有利的转角序列与转角侧翼Trp/Trp相互作用以及骨架酰胺和i - 2 Trp环之间的C-末端H-键合相互作用组合，产生特别稳定的（ΔGU > 7 kJ/mol）截短发夹，Ac-WI-（D-Pro-D-Asn）-KWTG-NH 2。在该构建体和其他在严重截短的发夹中具有W-（4-残基转角）-W基序的构建体中，C-末端Trp是明确定义的面对边（FtE）芳基/芳基相互作用中的边缘残基。较长的发夹和具有六个残基转角的发夹保留了首次在trpzip肽中观察到的反向“边对面”Trp/Trp几何形状。突变研究表明，W-（4-残基转角）-W相互作用提供了至少3 kJ/mol的稳定性，超过了由于Trp更大的β-倾向所导致的稳定性。Trp的β-倾向依赖于环境;但是，对于所研究的系统，总是大于Thr的β-倾向（0.4 - 4.7 kJ/mol）。在非H键合的位置远程的转折，两个替代的边缘到面的几何形状被观察到，并没有证据表明，由于色氨酸/色氨酸相互作用的额外的稳定。定义了边-面Trp/Trp、Trp/Lys π-阳离子和Trp/Gly-HN相互作用的NMR结构位移诊断。后者可以在发夹的匝（n = 2）和C-末端（n = 1）处引起-WXnG-单元中的Gly-HN的> 3 ppm的高场位移。末端YTG单位导致稍微较小的位移（对于100%折叠外推至2 ppm）。在具有EtF和FtE W/W相互作用几何结构的肽中，Trp至Tyr的突变表明Trp是芳基/芳基配对中的优选“面”残基，推测是由于其更大的π碱性。
By combining a favorable turn sequence with a turn flanking Trp/Trp interaction and a C-terminal H-bonding interaction between a backbone amide and an i - 2 Trp ring, a particularly stable (ΔGU > 7 kJ/mol) truncated hairpin, Ac-WI-(D-Pro-D-Asn)-KWTG-NH2, results. In this construct and others with a W-(4-residue turn)-W motif in severely truncated hairpins, the C-terminal Trp is the edge residue in a well-defined face-to-edge (FtE) aryl/aryl interaction. Longer hairpins and those with six-residue turns retain the reversed “edge-to-face” Trp/Trp geometry first observed for the trpzip peptides. Mutational studies suggest that the W-(4-residue turn)-W interaction provides at least 3 kJ/mol of stabilization in excess of that due to the greater β-propensity of Trp. The β-propensity of Trp is context dependent; but, for the systems studied, always greater than that of Thr (by 0.4 - 4.7 kJ/mol). At non-H-bonded positions remote from the turn, two alternative edge-to-face geometries are observed and there is no evidence of additional stabilization due to the Trp/Trp interaction. The NMR structuring shift diagnostics of edge-to-face Trp/Trp, Trp/Lys π-cation, and Trp/Gly-HN interactions have been defined. The latter can give rise to > 3 ppm upfield shifts for the Gly-HN in -WXnG- units both in turns (n = 2) and at the C-termini (n = 1) of hairpins. Terminal YTG units result in somewhat smaller shifts (extrapolated to 2 ppm for 100% folding). In peptides with both the EtF and FtE W/W interaction geometries, Trp to Tyr mutations indicate that Trp is the preferred “face” residue in aryl/aryl pairings, presumably due to its greater π basicity.
登录
查看更多内容
影响因子：
15
作者：
Andersen, Niels H.;Olsen, Katherine A.;Farazi, Shabnam R.
通讯作者：
Farazi, Shabnam R.
影响因子：
56.9
作者：
Dahiyat, BI;Mayo, SL
通讯作者：
Mayo, SL
影响因子：
15
作者：
Butterfield, SM;Cooper, WJ;Waters, ML
通讯作者：
Waters, ML
影响因子：
2.9
作者：
Aravinda, S;Harini, VV;Balaram, P
通讯作者：
Balaram, P
DOI：
10.1016/s1359-0278(96)00022-3
发表时间：
1996-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
deAlba, E;Jimenez, MA;Nieto, JL
通讯作者：
Nieto, JL