Aspergillus niger protein EstA defines a new class of fungal esterases within the α/β hydrolase fold superfamily of proteins
Aspergillus niger protein EstA defines a new class of fungal esterases within the α/β hydrolase fold superfamily of proteins
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DOI：
10.1016/j.str.2004.03.005
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发表时间：
2004-04-01
期刊：
影响因子：
5.7
通讯作者：
Marchot, P
中科院分区：
文献类型：
--
作者：
Bourne, Y;Hasper, AA;Marchot, P
从真菌尼日尔，我们确定了一个新的基因编码蛋白EstA，α/β-水解酶折叠超家族的成员，但未知的底物特异性。EstA被过表达，其晶体结构通过使用脂肪酶乙酰胆碱酯酶嵌合体模板的分子置换来解决。EstA的2.1 A解析结构揭示了典型的Ser/Glu/ His催化三联体，位于溶剂可接近的大型碗状空腔底部的一个小口袋中。测定通过手动对接程序选择的潜在底物的EstA活性。与口袋的几何形状一致，优先水解短酰基/丙基链substrates被found. Identification从其他真菌，其中一些是广泛的宿主范围的病原体的基因组中的密切同系物，定义EstA作为一类新的真菌酯酶的超家族内的第一个成员。因此，EstA的结构构成了设计针对其致病同源物的新抗真菌剂的主要模板。
From the fungus Aspergillus niger, we identified a new gene encoding protein EstA, a member of the alpha/beta-hydrolase fold superfamily but of unknown substrate specificity. EstA was overexpressed and its crystal structure was solved by molecular replacement using a lipaseacetylcholinesterase chimera template. The 2.1 A resolution structure of EstA reveals a canonical Ser/Glu/ His catalytic triad located in a small pocket at the bottom of a large solvent-accessible, bowl-shaped cavity. Potential substrates selected by manual docking procedures were assayed for EstA activity. Consistent with the pocket geometry, preference for hydrolysis of short acyl/propyl chain substrates was found. Identification of close homologs from the genome of other fungi, of which some are broad host-range pathogens, defines EstA as the first member of a novel class of fungal esterases within the superfamily. Hence the structure of EstA constitutes a lead template in the design of new antifungal agents directed toward its pathogenic homologs.