Structure of arylamine N-acetyltransferase from Mycobacterium tuberculosis determined by cross-seeding with the homologous protein from M. marinum: triumph over adversity
Structure of arylamine N-acetyltransferase from Mycobacterium tuberculosis determined by cross-seeding with the homologous protein from M. marinum: triumph over adversity
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DOI：
10.1107/s0907444913015126
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发表时间：
2013-08-01
影响因子：
2.2
通讯作者：
Garman, Elspeth F.
中科院分区：
文献类型：
--
作者：
Abuhammad, Areej;Lowe, Edward D.;Garman, Elspeth F.
结核分枝杆菌芳基胺N-乙酰转移酶（TBNAT）在巨噬细胞内微生物的存活中起重要作用。药物化学的努力，以优化抑制剂的TBNAT酶已受到阻碍，缺乏一个三维结构的酶。本文采用交叉接种法制备了TBNAT的一级结构。据报道，Marinum。尽管这两种酶之间的相似性（74%的序列同一性），他们表现出不同的物理和生化特性。该结构优雅地揭示了蛋白质表面的特征以及与药物发现工作相关的TBNAT活性位点的细节。衍射数据的晶体学分析提出了许多挑战，因为晶体是孪生的并且习惯具有伪平移对称性。
Arylamine N-acetyltransferase from Mycobacterium tuberculosis (TBNAT) plays an important role in the intracellular survival of the microorganism inside macrophages. Medicinal chemistry efforts to optimize inhibitors of the TBNAT enzyme have been hampered by the lack of a three-dimensional structure of the enzyme. In this paper, the first structure of TBNAT, determined using a lone crystal produced using cross-seeding with the homologous protein from M. marinum, is reported. Despite the similarity between the two enzymes (74% sequence identity), they show distinct physical and biochemical characteristics. The structure elegantly reveals the characteristic features of the protein surface as well as details of the active site of TBNAT relevant to drug-discovery efforts. The crystallographic analysis of the diffraction data presented many challenges, since the crystal was twinned and the habit possessed pseudo-translational symmetry.