Flexibility and communication within the structure of the Mycobacterium smegmatis methionyl-tRNA synthetase
Flexibility and communication within the structure of the Mycobacterium smegmatis methionyl-tRNA synthetase
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DOI：
10.1111/j.1742-4658.2010.07784.x
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发表时间：
2010-10-01
期刊：
影响因子：
5.4
通讯作者：
Unge, Torsten
中科院分区：
文献类型：
--
作者：
Ingvarsson, Henrik;Unge, Torsten
分别在 2.3 A 和 2.8 A 下通过 X 射线晶体学分析来自耻垢分枝杆菌的与配体甲硫氨酸/腺苷和甲硫氨酸复合的单体甲硫氨酰-tRNA 合成酶的两种结构。该结构证明了多域酶的灵活性。鉴定出结构的新构象，其中连接肽结构域与催化结构域的结合比之前描述的更紧密。我们结构中的 KMSKS(301-305) 环处于开放且非活性构象，与之前的结构不同，环围绕位于 Asn297 和 Val310 的铰链旋转约 90 度。腺苷与甲硫氨酰-tRNA 合成酶甲硫氨酸复合物的结合导致 KMSKS 结构域发生变化，使其更接近催化结构域。评估了腺苷结合位点用于抑制剂结合的潜在用途，并鉴定了特定变构抑制剂的潜在结合位点。
Two structures of monomeric methionyl-tRNA synthetase, from Mycobacterium smegmatis, in complex with the ligands methionine/adenosine and methionine, were analyzed by X-ray crystallography at 2.3 A and at 2.8 A, respectively. The structures demonstrated the flexibility of the multidomain enzyme. A new conformation of the structure was identified in which the connective peptide domain bound more closely to the catalytic domain than described previously. The KMSKS(301-305) loop in our structures was in an open and inactive conformation that differed from previous structures by a rotation of the loop of about 90 degrees around hinges located at Asn297 and Val310. The binding of adenosine to the methionyl-tRNA synthetase methionine complex caused a shift in the KMSKS domain that brought it closer to the catalytic domain. The potential use of the adenosine-binding site for inhibitor binding was evaluated and a potential binding site for a specific allosteric inhibitor was identified.