Characterization of a novel type VII β-turn conformation for a bio-active tetrapeptide rigin -: A synergy between theoretical and experimental results

被引:11
作者
Ashish [1 ]
Grover, A [1 ]
Kishore, R [1 ]
机构
[1] Inst Microbial Technol, Chandigarh 160036, India
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 2000年 / 267卷 / 05期
关键词
rigin; peptide immunomodulator; molecular dynamics simulations; H-1 NMR spectroscopy; type VII beta-turn structure;
D O I
10.1046/j.1432-1327.2000.01144.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The conformational analysis of an immunomodulating tetrapeptide rigin (H-Gly-Gln-Pro-Arg-OH), shown to possess diverse immunological activity, has been investigated both theoretically and experimentally for its conformational preferences. Unrestrained molecular dynamics simulation studies in implicit dimethylsulfoxide provide strong support for the existence of a significant population of ordered reverse turn structures for the major trans isomer. Of the three different energy minimized families, generated from computer molecular modelling, only one could be complemented by most of the 1D and 2D H-1 NMR parameters obtained in dimethylsulfoxide-d(6). A variable temperature NMR experiment in dimethylsulfoxide-d(6) revealed that the preferred conformation is not stabilized by an intramolecular hydrogen bonding interaction. An analysis of the 2D ROESY experiment provides evidence in favour of an uncommonly observed, rather ill-defined type VII beta-turn structure. A survey of the observed specific inter-and intra-residue NOE connectivities and their comparison with one of the predicted low-energy conformations, demonstrates synergy between the theoretical molecular modelling and experimentally determined NMR spectral data. The primary structure, rather than long-range interactions, appears to be critical in determining the folding behaviour of the bio-active rigin. The present structural attributes may be valuable in peptide drug design and development of the rigin analogs having more effective stimulating activity.
引用
收藏
页码:1455 / 1463
页数:9
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