Galzitskaya O, Caflisch A
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russian Federation.
J Mol Graph Model. 1999 Feb;17(1):19-27. doi: 10.1016/s1093-3263(99)00017-0.
Phakellistatin 8 is a cyclic decapeptide that inhibits cancer cell growth and has sequence and structure similar to antamanide. In molecular dynamics simulations of phakellistatin 8 in water, the decapeptide ring undergoes a conformational change from the saddle-like crystal structure to a more elongated conformation by a transition of the Tyr9 main chain from the alpha L to an extended structure. This is coupled to the loss of the NH9-O6 beta-turn hydrogen bond and the transient dissociation of the Pro7-Tyr9 side-chain packing. Furthermore, the water molecule acting as a transannular bridge forms an additional hydrogen bond with phakellistatin 8, namely with the NH group of Val5 besides those already present in the crystal structure, i.e., with the NH of Ile10 and the CO of Leu6. The alpha-turn hydrogen bond between the Phe4 amide hydrogen and the Ile10 carbonyl oxygen is always present. The solution conformations of the two cyclic decapeptides are similar, in particular in the region involving the NH4-O10 alpha turn of phakellistatin 8 and the NH5-O1 alpha turn of antamanide. The simulation results suggest that in aqueous solution the conformation of phakellistatin 8 is more extended than in the crystalline state, and on a nanosecond time scale phakellistatin 8 is more flexible than antamanide.
海兔抑素8是一种环状十肽，可抑制癌细胞生长，其序列和结构与抗毒环肽相似。在海兔抑素8在水中的分子动力学模拟中，十肽环通过Tyr9主链从αL构象转变为伸展结构，从鞍状晶体结构转变为更细长的构象。这伴随着NH9-O6β-转角氢键的丧失以及Pro7-Tyr9侧链堆积的瞬时解离。此外，作为跨环桥的水分子与海兔抑素8形成了额外的氢键，即除了晶体结构中已存在的与Ile10的NH和Leu6的CO形成的氢键外，还与Val5的NH基团形成氢键。Phe4酰胺氢与Ile10羰基氧之间的α-转角氢键始终存在。这两种环状十肽的溶液构象相似，特别是在涉及海兔抑素8的NH4-O10α-转角和抗毒环肽的NH5-O1α-转角的区域。模拟结果表明，在水溶液中，海兔抑素8的构象比在晶体状态下更伸展，并且在纳秒时间尺度上，海兔抑素8比抗毒环肽更灵活。
