Structures of Cyanobactin Maturation Enzymes Define a Family of Transamidating Proteases
Structures of Cyanobactin Maturation Enzymes Define a Family of Transamidating Proteases
复制标题
DOI：
10.1016/j.chembiol.2012.09.012
复制
发表时间：
2012-11-21
影响因子：
--
通讯作者：
Nair, Satish K.
中科院分区：
文献类型：
--
作者：
Agarwal, Vinayak;Pierce, Elizabeth;Nair, Satish K.
蓝藻菌素是一类核糖体编码的大环天然产物，通过蛋白质水解加工和随后的核糖体肽前体N-C大环化生物合成。大环化通过两步过程发生，其中第一个蛋白酶（PatA）从前体中去除氨基末端的侧翼序列，产生前体肽的游离N端，第二个蛋白酶（PatG）去除c末端的侧翼序列，然后催化转酰胺反应产生N- c环化产物。在这里，我们展示了PatA和PatG来自patellamide团簇以及PagA来自prenylagaramide团簇的蛋白酶结构域的晶体结构。转氨化PatG蛋白酶的比较结构和生化分析表明，存在一个独特的结构元件，不同于典型的枯草菌素蛋白酶，这可能有助于肽底物的N-C大环化。
Cyanobactins, a class of ribosomally encoded macrocylic natural products, are biosynthesized through the proteolytic processing and subsequent N-C macrocylization of ribosomal peptide precursors. Macrocylization occurs through a two-step process in which the first protease (PatA) removes the amino terminal flanking sequence from the precursor to yield a free N terminus of the precursor peptide, and the second protease (PatG) removes the C-terminal flanking sequence and then catalyzes the transamidation reaction to yield an N-C cyclized product. Here, we present the crystal structures of the protease domains of PatA and PatG from the patellamide cluster and of PagA from the prenylagaramide cluster. A comparative structural and biochemical analysis of the transamidating PatG protease reveals the presence of a unique structural element distinct from canonical subtilisin proteases, which may facilitate the N-C macrocylization of the peptide substrate.