Smith Leif, Zachariah Cherian, Thirumoorthy Ramanan, Rocca Jim, Novák Jan, Hillman J D, Edison Arthur S
University of Florida Interdisciplinary Graduate Program in Neuroscience, Gainesville, Florida 32611, USA.
Biochemistry. 2003 Sep 9;42(35):10372-84. doi: 10.1021/bi034490u.
Mutacin 1140 is a member of a family of ribosomally synthesized peptide bacteriocins called lantibiotics (lanthionine-containing antibiotics) and is produced by the Gram-positive bacterium Streptococcus mutans. Mutacin 1140 has been shown to be effective against a broad array of Gram-positive bacteria. Chromatography and mass spectroscopy data suggested that mutacin 1140 forms a small compact structure. Nuclear magnetic resonance (NMR) data and restrained molecular dynamics simulations showed that mutacin 1140 interconverts between multiple structures. Calculations of scalar (J) coupling constants showed the best agreement with experimental values when the entire population-weighted ensemble of structures was used, providing independent support for the ensemble. Representative structures from each major group in the ensemble had a common feature in which they are all kinked around the hinge region forming a horseshoe-like shape, and the regions of flexibility of the molecule were limited and well-defined. The structures determined in this study provide a starting point for modeling the mutacin 1140-membrane interactions and pore formation.
变链菌素1140是一类由核糖体合成的肽类细菌素（含羊毛硫氨酸的抗生素）家族的成员，由革兰氏阳性细菌变形链球菌产生。已证明变链菌素1140对多种革兰氏阳性细菌有效。色谱和质谱数据表明，变链菌素1140形成一种小的致密结构。核磁共振（NMR）数据和受限分子动力学模拟表明，变链菌素1140在多种结构之间相互转换。当使用整个群体加权结构集合时，标量（J）耦合常数的计算与实验值显示出最佳一致性，为该集合提供了独立支持。该集合中每个主要组的代表性结构都有一个共同特征，即它们都在铰链区域附近弯曲形成马蹄形，并且分子的柔性区域有限且定义明确。本研究中确定的结构为模拟变链菌素1140与膜的相互作用和孔形成提供了一个起点。
