Yu L, Petros A M, Schnuchel A, Zhong P, Severin J M, Walter K, Holzman T F, Fesik S W
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Nat Struct Biol. 1997 Jun;4(6):483-9. doi: 10.1038/nsb0697-483.
The Erm family of methyltransferases is responsible for the development of resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics. These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS antibiotics from binding to the ribosome and exhibiting their antibacterial activity. Here we describe the three-dimensional structure of an Erm family member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM is structurally similar to that found in other methyltransferases and consists of a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded beta-sheet. In contrast to the catalytic domain, the substrate binding domain is different from other methyltransferases and adopts a novel fold that consists of four alpha-helices.
Erm甲基转移酶家族负责对大环内酯-林可酰胺-链阳菌素B（MLS）类抗生素产生耐药性。这些酶使23S核糖体RNA的一个腺嘌呤甲基化，从而阻止MLS类抗生素与核糖体结合并发挥其抗菌活性。在此，我们描述了通过核磁共振光谱法测定的Erm家族成员ErmAM的三维结构。ErmAM的催化结构域在结构上与其他甲基转移酶中的催化结构域相似，由一个七链β折叠片层组成，两侧为α螺旋和一个小的双链β折叠片层。与催化结构域不同，底物结合结构域与其他甲基转移酶不同，采用了一种由四个α螺旋组成的新型折叠结构。
