Department of Biochemistry, Osaka Medical College, Takatsuki, Japan.
Japan Synchrotron Radiation Research Institute (JASRI), SPring-8, Sayo, Japan.
FEBS Lett. 2018 May;592(9):1611-1619. doi: 10.1002/1873-3468.13050. Epub 2018 Apr 22.
The DNA mismatch repair endonuclease MutL consists of N-terminal ATPase and C-terminal endonuclease domains. The endonuclease domain binds zinc ion, although the ion seems not to function as a catalytic metal ion. Here, we solved the crystal structures of the Aquifex aeolicus MutL (aqMutL) endonuclease domain complexed with a single and three zinc ions. Differences between the two structures show that binding of multiple zinc ions induces a closed-to-open conformational change at the catalytic site. It is also revealed that the three-zinc-bound form of the endonuclease domain exhibits higher endonuclease activity than the single-zinc-bound form. These results indicate that multiple zinc ions are required for the proper folding of the endonuclease domain, which would facilitate the endonuclease activity of aqMutL.
DNA 错配修复内切酶 MutL 由 N 端 ATP 酶和 C 端内切酶结构域组成。内切酶结构域结合锌离子，尽管该离子似乎不作为催化金属离子发挥作用。在这里，我们解析了与单个和三个锌离子结合的 Aquifex aeolicus MutL（aqMutL）内切酶结构域的晶体结构。两种结构之间的差异表明，多个锌离子的结合诱导催化部位的闭合到开放构象变化。还揭示了内切酶结构域的三锌结合形式比单锌结合形式具有更高的内切酶活性。这些结果表明，多个锌离子是内切酶结构域正确折叠所必需的，这将有助于 aqMutL 的内切酶活性。
