ABSTRACT

Acetyl Coenzyme A Carboxylase (AccD6) is a homodimeric protein which is involved in the carboxylation of acetyl coenzyme A to produce malonyl coenzyme A, which plays an important role in the biosynthesis of fatty acid chain. However, studies suggest that AccD6 in combination with AccA3 produces malonyl co-A. Certain herbicides are known to inhibit plant ACC. Among these herbicides, haloxyfop was found to inhibit AccD6 at IC50 of 21.1 ± 1 µM. In this study, we have performed molecular docking of the Maybridge database consisting of ~55,000 compounds in the active site of the protein with haloxyfop as a reference molecule, followed by molecular dynamics study and biological activity determination of prioritized compounds. Out of the nine compounds selected for biological evaluation, three compounds – CD07230, HTS08529 and KM08871 – were found to exhibit anti-mycobacterial activity.

摘要

乙酰辅酶A羧化酶（AccD6）是一种同二聚体蛋白，参与乙酰辅酶A的羧化反应以生成丙二酰辅酶A，丙二酰辅酶A在脂肪酸链的生物合成中起着重要作用。但是，研究表明AccD6与AccA3结合可产生丙二酰辅酶A。已知某些除草剂可抑制植物ACC。在这些除草剂中，发现haloxyfop抑制AccD6的IC50为21.1±1 µM。在这项研究中，我们已经进行了Maybridge数据库的分子对接，该数据库由在蛋白质的活性位点中约55,000种化合物组成，并以haloxyfop作为参考分子，然后进行了分子动力学研究和确定优先化合物的生物活性。在用于生物学评估的9种化合物中，有3种化合物– CD07230，