Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Japan; Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Japan; Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Biochim Biophys Acta Proteins Proteom. 2018 Jul;1866(7):783-788. doi: 10.1016/j.bbapap.2018.01.006. Epub 2018 Jan 11.
Recently, non-enzymatic stereoinversions of aspartic acid (Asp) residues in proteins and peptides have been reported. Here, we performed replica exchange molecular dynamics (REMD) simulations of model peptides (exon 6, 26A-1, and 26A-2) extracted from elastin to investigate their structural features, thereby revealing the factor that influences stereoinversions. For REMD trajectories, we calculated distances between carboxyl carbon in Asp and amide nitrogen in the (n + 1) residue (CN distances). Because bond formation between carbon and nitrogen is indispensable to the formation of a succinimide intermediate the distance between them seems to play an important role in stereoinversion. Moreover, we calculated polar surface areas (PSAs) for the trajectories, finding that CN distances and PSA were different for each peptide, with the longest CN distance and smallest PSA observed for exon 6 peptide, where stereoinversion of Asp is the slowest. Although the average CN distance was shorter for exon 26A-1 peptide than for exon 26A-2 peptide, the number of conformations with CN distances <3.0 Å was greater for exon 26A-2 peptide than for exon 26A-1 peptide. Furthermore, PSA for amide nitrogen of the (n + 1) residue was larger for exon 26A-2 peptide than for exon 26A-1 peptide. These results indicated that the flexibility of Asp and (n + 1) residues and hydrophilicity of peptides, especially in the (n + 1) residue, play important roles in the stereoinversion of Asp. This article is part of a Special Issue entitled: D-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.
最近，已有研究报道蛋白质和肽中天冬氨酸（Asp）残基的非酶立体反转。在这里，我们对弹性蛋白中提取的模型肽（外显子 6、26A-1 和 26A-2）进行了复制交换分子动力学（REMD）模拟，以研究它们的结构特征，从而揭示影响立体反转的因素。对于 REMD 轨迹，我们计算了 Asp 的羧基碳与（n+1）位酰胺氮之间的距离（CN 距离）。因为碳氮键的形成对于形成琥珀酰亚胺中间体是必不可少的，所以它们之间的距离似乎在立体反转中起着重要作用。此外，我们还计算了轨迹的极性表面积（PSA），发现每个肽的 CN 距离和 PSA 都不同，exon 6 肽的 CN 距离最长，PSA 最小，Asp 的立体反转最慢。虽然 exon 26A-1 肽的平均 CN 距离比 exon 26A-2 肽短，但 CN 距离<3.0Å的构象数量exon 26A-2 肽比 exon 26A-1 肽多。此外，exon 26A-2 肽的（n+1）位酰胺氮的 PSA 比 exon 26A-1 肽大。这些结果表明，Asp 和（n+1）位残基的灵活性以及肽的亲水性，特别是在（n+1）位残基中，对 Asp 的立体反转起着重要作用。本文是由 Loredano Pollegioni 博士、Jean-Pierre Mothet 博士和 Molla Gianluca 博士编辑的特刊“D-氨基酸：镜像中的生物学”的一部分。
