Biomacromolecules. 2018 Jul 9;19(7):2650-2656. doi: 10.1021/acs.biomac.8b00254. Epub 2018 May 1.
Enzymes possess unique qualities that make them ideal regulators of supramolecular assembly. They are uniquely sensitive to biomolecules and biological compartments, catalytic in effecting chemical reactions, and present a biocompatible and degradable platform for assembly regulation. We demonstrate the novel utility of Histidine Triad Nucleotide Binding Protein 1 (HINT1) in regulating supramolecular hydrogel formation. We synthesized nucleoside-phosphoramidate-functionalized self-assembling peptides that we observed to form nanofibers. We found HINT1's catalytic hydrolysis of the nucleoside phosphoramidate moieties within the nanofiber structures to induce nanofiber organization and higher ordered assembly. The role of HINT1 in effecting this structural change was confirmed with experiments utilizing a high-affinity HINT1 inhibitor and catalytically dead HINT1 mutant. In addition, the kinetics and morphology of hydrogel formation were found to be dependent on the structure of the released nucleoside monophosphate. This work highlights the self-assembly of phosphoramidate nanofibers and their higher organization triggered by HINT1 enzymatic activity.
酶具有独特的性质，使其成为超分子组装的理想调节剂。它们对生物分子和生物区室具有独特的敏感性，在催化化学反应方面具有效果，并且为组装调节提供了生物兼容和可降解的平台。我们展示了组氨酸三核苷酸结合蛋白 1 (HINT1) 在调节超分子水凝胶形成中的新用途。我们合成了核苷-磷酰胺基功能化的自组装肽，观察到它们形成纳米纤维。我们发现 HINT1 对纳米纤维结构内核苷磷酰胺部分的催化水解诱导纳米纤维组织和更高阶组装。利用高亲和力 HINT1 抑制剂和催化失活 HINT1 突变体进行的实验证实了 HINT1 在产生这种结构变化中的作用。此外，水凝胶形成的动力学和形态取决于释放的核苷单磷酸的结构。这项工作强调了磷酰胺纳米纤维的自组装及其由 HINT1 酶活性触发的更高组织。
