Pani Giovanna, Dessì Alessandro, Dallocchio Roberto, Scherm Barbara, Azara Emanuela, Delogu Giovanna, Migheli Quirico
Dipartimento di Agraria and Unità di Ricerca Istituto Nazionale di Biostrutture e Biosistemi, Università degli Studi di Sassari, Viale Italia 39, I-07100, Sassari, Italy.
Istituto CNR di Chimica Biomolecolare, Traversa La Crucca 3, I-07100, Sassari, Italy.
PLoS One. 2016 Jun 13;11(6):e0157316. doi: 10.1371/journal.pone.0157316. eCollection 2016.
A model of the trichodiene synthase (TRI5) of the wheat fungal pathogen and type-B trichothecene producer Fusarium culmorum was developed based on homology modelling with the crystallized protein of F. sporotrichioides. Eight phenolic molecules, namely ferulic acid 1, apocynin 2, propyl gallate 3, eugenol 4, Me-dehydrozingerone 5, eugenol dimer 6, magnolol 7, and ellagic acid 8, were selected for their ability to inhibit trichothecene production and/or fungal vegetative growth in F. culmorum. The chemical structures of phenols were constructed and partially optimised based on Molecular Mechanics (MM) studies and energy minimisation by Density Functional Theory (DFT). Docking analysis of the phenolic molecules was run on the 3D model of F. culmorum TRI5. Experimental biological activity, molecular descriptors and interacting-structures obtained from computational analysis were compared. Besides the catalytic domain, three privileged sites in the interaction with the inhibitory molecules were identified on the protein surface. The TRI5-ligand interactions highlighted in this study represent a powerful tool to the identification of new Fusarium-targeted molecules with potential as trichothecene inhibitors.
基于与禾谷镰刀菌结晶蛋白的同源建模，构建了小麦真菌病原体和B型单端孢霉烯产生菌禾谷镰刀菌的三烯合成酶（TRI5）模型。选择了8种酚类分子，即阿魏酸1、鱼藤酮2、没食子酸丙酯3、丁香酚4、甲基脱氢姜酮5、丁香酚二聚体6、厚朴酚7和鞣花酸8，因其具有抑制禾谷镰刀菌中单端孢霉烯产生和/或真菌营养生长的能力。基于分子力学（MM）研究和密度泛函理论（DFT）的能量最小化，构建并部分优化了酚类化合物的化学结构。在禾谷镰刀菌TRI5的三维模型上进行了酚类分子的对接分析。比较了从计算分析中获得的实验生物活性、分子描述符和相互作用结构。除了催化结构域，在蛋白质表面还确定了与抑制分子相互作用的三个特殊位点。本研究中突出的TRI5-配体相互作用是鉴定具有作为单端孢霉烯抑制剂潜力的新型靶向镰刀菌分子的有力工具。
