Prasch T, Naumann T, Markert R L, Sattler M, Schubert W, Schaal S, Bauch M, Kogler H, Griesinger C
Institut für Organische Chemie, Johann Wolfgang Goethe-Universität Frankfurt, Germany.
Eur J Biochem. 1997 Mar 1;244(2):501-12. doi: 10.1111/j.1432-1033.1997.00501.x.
The solution structure of the tetracyclic lantibiotic mersacidin in methanol (CD3OH) has been determined by NMR followed by distance bound driven dynamics and subsequent restrained molecular dynamics simulations combined with an iterative relaxation matrix approach and alternatively by a simulated annealing protocol. The molecular dynamics simulations were performed with the AMBER program system and with the INSIGHT program package. The distance bound driven dynamics calculation was conducted using a modified version of the DISGEO II program. The interproton distance restraints were derived from jump symmetrized rotating-frame Overhauser enhancement and exchange (JS-ROESY) spectra, which yield optimum sensitivity for medium-sized molecules like mersacidin. The connectivities via the sulfide bridges were unambiguously confirmed by heteronuclear NMR techniques (heteronuclear single quantum coherence and heteronuclear multiple bond correlation methods). Due to the tetracyclic structure, mersacidin exhibits a rather rigid globular shape, which neither belongs to the duramycin nor to the nisin structure type lantibiotics. The resulting structures for the simulated annealing protocol of restrained and subsequent free molecular dynamics were compared and found to be very similar.
四环羊毛硫抗生素梅萨西丁在甲醇（CD3OH）中的溶液结构已通过核磁共振确定，随后进行距离约束驱动动力学以及随后的受限分子动力学模拟，并结合迭代弛豫矩阵方法，也可通过模拟退火协议确定。分子动力学模拟使用AMBER程序系统和INSIGHT程序包进行。距离约束驱动动力学计算使用DISGEO II程序的修改版本进行。质子间距离约束来自跳跃对称旋转框架Overhauser增强和交换（JS-ROESY）光谱，该光谱对像梅萨西丁这样的中等大小分子具有最佳灵敏度。通过异核核磁共振技术（异核单量子相干和异核多键相关方法）明确证实了通过硫桥的连接性。由于四环结构，梅萨西丁呈现出相当刚性的球状形状，它既不属于短杆菌肽，也不属于乳链菌肽结构类型的羊毛硫抗生素。比较了受限和随后自由分子动力学模拟退火协议的所得结构，发现它们非常相似。
