School of Life Sciences (KNU Creative BioResearch Group), KNU Institute for Microorganisms, Kyungpook National University, Daegu, 41566, Republic of Korea.
School of Life Sciences (KNU Creative BioResearch Group), KNU Institute for Microorganisms, Kyungpook National University, Daegu, 41566, Republic of Korea.
Biochem Biophys Res Commun. 2019 Sep 24;517(3):399-406. doi: 10.1016/j.bbrc.2019.07.117. Epub 2019 Aug 1.
Mycobacterium smegmatis is a good model for studying the physiology and pathogenesis of Mycobacterium tuberculosis due to its genetic similarity. As methionine biosynthesis exists only in microorganisms, the enzymes involved in methionine biosynthesis can be a potential target for novel antibiotics. Homoserine O-acetyltransferase from M. smegmatis (MsHAT) catalyzes the transfer of acetyl-group from acetyl-CoA to homoserine. To investigate the molecular mechanism of MsHAT, we determined its crystal structure in apo-form and in complex with either CoA or homoserine and revealed the substrate binding mode of MsHAT. A structural comparison of MsHAT with other HATs suggests that the conformation of the α5 to α6 region might influence the shape of the dimer. In addition, the active site entrance shows an open or closed conformation and might determine the substrate binding affinity of HATs.
耻垢分枝杆菌由于其遗传相似性，是研究结核分枝杆菌生理和发病机制的良好模型。由于甲硫氨酸生物合成仅存在于微生物中，因此参与甲硫氨酸生物合成的酶可以成为新型抗生素的潜在靶标。来自耻垢分枝杆菌的同型丝氨酸 O-乙酰基转移酶（MsHAT）催化乙酰辅酶 A 上的乙酰基转移到同型丝氨酸上。为了研究 MsHAT 的分子机制，我们测定了其在 apo 形式和与 CoA 或同型丝氨酸复合物中的晶体结构，并揭示了 MsHAT 的底物结合模式。与其他 HAT 的结构比较表明，α5 到 α6 区域的构象可能会影响二聚体的形状。此外，活性位点入口显示出开放或关闭构象，并且可能决定 HAT 的底物结合亲和力。
