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尿卟啉原Ⅲ合酶的生物医学应用。

Biomedical Applications of Lumazine Synthase.

机构信息

Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047; Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047.

Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047.

出版信息

J Pharm Sci. 2018 Sep;107(9):2283-2296. doi: 10.1016/j.xphs.2018.05.002. Epub 2018 May 12.

Abstract

Lumazine synthase (LS) is a family of enzyme involved in the penultimate step in the biosynthesis of riboflavin. Its enzymatic mechanism has been well defined, and many LS structures have been solved using X-ray crystallography or cryoelectron microscopy. LS is composed of homooligomers, which vary in size and subunit number, including pentamers, decamers, and icosahedral sixty-mers, depending on its species of origin. Research on LS has expanded beyond the initial focus on its enzymatic function to properties related to its oligomeric structure and exceptional conformational stability. These attributes of LS systems have now been repurposed for use in various biomedical fields. This review primarily focuses on the applications of LS as a flexible vaccine presentation system. Presentation of antigens on the surface of LS results in a high local concentration of antigens displayed in an ordered array. Such repetitive structures enable the cross-linking of B-cell receptors and result in strong immune responses through an avidity effect. Potential issues with the use of this system and corresponding solutions are also discussed with the objective of improved utilization of the LS system in vaccine development.

摘要

荧光素合酶(LS)是参与核黄素生物合成最后一步的酶家族。其酶促机制已经得到很好的定义,并且已经使用 X 射线晶体学或冷冻电子显微镜解决了许多 LS 结构。LS 由同寡聚体组成,其大小和亚基数量不同,包括五聚体、十聚体和二十面体六十聚体,具体取决于其来源的物种。LS 的研究已经超出了最初对其酶功能的关注,扩展到与寡聚体结构和异常构象稳定性相关的性质。LS 系统的这些特性现已被重新用于各种生物医学领域。本综述主要关注 LS 作为一种灵活的疫苗呈递系统的应用。将抗原呈现在 LS 的表面会导致在有序排列中显示出高浓度的抗原。这种重复结构能够交联 B 细胞受体,并通过亲合力效应产生强烈的免疫反应。还讨论了使用该系统的潜在问题和相应的解决方案,目的是改善 LS 系统在疫苗开发中的利用。

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