NADP-dependent glutamate dehydrogenases in a dimorphic zygomycete Benjaminiella poitrasii: Purification, characterization and their evaluation as an antifungal drug target
作者:Ejaj K. Pathan、Anand M. Kulkarni、Nallaballe V.L. Prasanna、Chepuri V. Ramana、Mukund V. Deshpande
DOI:10.1016/j.bbagen.2020.129696
日期:2020.11
characterized. The structural analogs of L-glutamate, dimethyl esters of isophthalic acid (DMIP) and its derivatives were designed, synthesized and screened for inhibition of NADP-GDH activity as well as YH transition in B. poitrasii, and also in human pathogenic Candida albicans strains. Results The BpNADPGDH I and BpNADPGDH II were found to be homo-hexameric proteins with native molecular mass of 282 kDa
背景 据报道,编码NADP依赖性谷氨酸脱氢酶(NADP-GDHs )的基因在酵母菌Benjaminiella poitrasii中显示出与酵母-菌丝(Y H)可逆转变的因果关系。由于Y H过渡对于人类病原性真菌在宿主中的存活和增殖具有重要意义,因此可以将NADP-GDHs用作抗真菌药物的靶标。 方法 通过在大肠杆菌BL-21细胞中的异源表达,纯化了芽孢杆菌的酵母形式特异性BpNADPGDH I和菌丝形式特异性BpNADPGDH II并进行了表征。设计,合成和筛选了L-谷氨酸,间苯二甲酸二甲酯(DMIP)及其衍生物的结构类似物,以抑制NADP-GDH活性以及Poitrasii以及人致病性白色念珠菌中的Y H转变。株。 结果 发现BpNADPGDH I和BpNADPGDH II是天然分子量分别为282 kDa和298 kDa,亚基分子量分别为47 kDa和49 kDa的同六聚体蛋白。除了独特的动力学特性外,还发现BpNADPGDH