基于昆虫几丁质酶结构的抑制剂筛选
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- 英文论文题名：Structure-based inhibitor screen of insect chitinase
- 论文作者：姜熙 ; 刘田 ; 杨青
- 英文论文作者：Xi Jiang ; Tian Liu ; Qing Yang ; School of Life Science and Biotechnology ; Dalian University of Technology
- 年：2016
- 作者机构：大连理工大学生命科学与技术学院;
- 论文关键词：昆虫 ; 蜕皮 ; 几丁质 ; 几丁质酶 ; 抑制剂
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：TQ450.1
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：206k
- 原文格式：D
- 会议级别：全国
摘要
昆虫的几丁质酶家族group Ⅰ主要负责蜕皮过程中表皮几丁质降解,被认为是农药设计的潜在靶标。通过分析亚洲玉米螟几丁质酶OfChtI催化域的晶体结构,发现其活性口袋底物结合裂缝处存在一系列芳香族氨基酸,提供其与底物结合的关键疏水作用,同时也是基于结构进行选择性抑制剂筛选的重要靶点~([1])。基于以上发现,通过对比底物几丁三糖化合物结构、电荷性质对商品化合物数据库进行虚拟筛选,获得了其抑制剂TP1,TP2。基于催化域底物结合口袋的空间结构对TP1,TP2衍生物进行第二轮筛选,获得了高活性高选择性的OfChtI抑制剂FQ3,其IC_(50)值为6.1μM。本研究为基于靶标结构的抑制剂设计提供了思路,也为针对昆虫蜕皮过程的绿色农药开发提供了先导化合物。
Small-molecule inhibitors against chitinases have potential applications as pesticides,fungicides,and antiasthmatics.We analyzed unliganded and oligosaccharide-complexed crystal structures of the insect chitinase OfChtI from Ostrinia furnacalis,which is essential to moulting,revealed that OfChtI contains a long substrate-binding cleft.Here,we based on the shape and electrostatic properties with three units of β-1,4-linked N-acetylglucosamine(GlcNAc)_3 to filter a library of ~million commercially available small molecules.Two compounds(TP1,TP2) was determined to be inhibitors of OfChtI.Then molecular docking was used to screen the TP series compounds.The best one is FQ3 with a IC_(50) value of 6.1 μM.
Small-molecule inhibitors against chitinases have potential applications as pesticides,fungicides,and antiasthmatics.We analyzed unliganded and oligosaccharide-complexed crystal structures of the insect chitinase OfChtI from Ostrinia furnacalis,which is essential to moulting,revealed that OfChtI contains a long substrate-binding cleft.Here,we based on the shape and electrostatic properties with three units of β-1,4-linked N-acetylglucosamine(GlcNAc)_3 to filter a library of ~million commercially available small molecules.Two compounds(TP1,TP2) was determined to be inhibitors of OfChtI.Then molecular docking was used to screen the TP series compounds.The best one is FQ3 with a IC_(50) value of 6.1 μM.
引文
[1]Lei,C.,Liu,T.,Yong,Z.,et al.,ACTA Crystallogr D.2014,70(4),932-942.