1.Development of VISTA in tumor immunotherapy
Yu ZHANG ; Fang YAN ; Yibei XIAO
Journal of China Pharmaceutical University 2022;53(4):400-409
V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a member of the B7 family that maintains homeostasis in T cells and myeloid cells.Blocking VISTA inhibits tumor development in in vitro and in vivo trials, and is an important target for tumor immunotherapy.This review focuses on its structural features, expression and biological functions in tumor microenvironment, summarizes the current stage of small molecule inhibitors and antibodies targeting VISTA, and discusses the research approaches.It aims to provide a rationale for subsequent study on VISTA and the development of related immune checkpoint antitumor drugs.
2.Structural feature of type I CRISPR-Cas system and its application in gene editing
Yuwen ZHANG ; Chenlin YU ; Xinchen DAI ; Yibei XIAO ; Meiling LU
Journal of China Pharmaceutical University 2021;52(6):675-683
The CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated) system is an "adaptive immune system" found in the genomes of bacteria and archaea which is mediated by RNA and resists foreign nucleic acid invasion.Take advantage of specific recognition of target nucleic acid, CRISPR-Cas system can efficiently edit their target site or accurately regulate gene expression, and now have been developed into a powerful tool for gene editing.According to the different compositions of the effector complex, the system has been divided into two categories: class 1 (type I, type IV, and type III) and class 2 (type II, type V, and type VI).Class 2 system, like the CRISPR-Cas9, is widely used in basic research due to the earliest discovery and best research.However, class 1 has not been maturely developed and utilized though it makes up 90% of the entire CRISPR-Cas system.In this essay, the classification of subtype, the assembly of Cascade complex, the cleavage and degradation mechanism of Cas3, and the application in gene editing of class 1 type I CRISPR-Cas system will be discussed and summarized to provide new ideas and methods for further mechanism studying and application of this category.
3.Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis.
Yucheng ZHAO ; Yuedong HE ; Liangliang HAN ; Libo ZHANG ; Yuanzheng XIA ; Fucheng YIN ; Xiaobing WANG ; Deqing ZHAO ; Sheng XU ; Fei QIAO ; Yibei XIAO ; Lingyi KONG
Acta Pharmaceutica Sinica B 2024;14(2):869-880
Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.