Hong Myoung-Ki, Lee Jung Hun, Kwon Dae Beom, Kim Jin-Kwang, Tran Thi-Huyen, Nguyen Dinh-Duc, Jeong Byeong Chul, Lee Sang Hee, Kang Lin-Woo
Department of Advanced Technology Fusion, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Oct 1;68(Pt 10):1226-8. doi: 10.1107/S1744309112035695. Epub 2012 Sep 28.
GIM-1 is a member of the class B carbapenemases (metallo-β-lactamases; MBLs) and has a wide spectrum of activity against carbapenems, penicillins and extended-spectrum cephalosporins, but not aztreonam. GIM-1 presents an enormous challenge to infection control, particularly in the eradication of Gram-negative pathogens including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii and nonfermenters. There are presently few or no drugs in late-stage development for these pathogens and GIM-1 is a potential target for the development of antimicrobial agents against pathogens producing MBLs. In this study, GIM-1 was cloned, overexpressed and crystallized. The GIM-1 crystals diffracted to 1.4 Å resolution and belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 38.5, b = 67.6, c = 72.8 Å. One molecule is present in the asymmetric unit, with a corresponding V(M) of 1.69 Å(3) Da(-1) and a solvent content of 27.1%.
GIM-1 是 B 类碳青霉烯酶(金属β-内酰胺酶;MBLs)的成员之一,对碳青霉烯类、青霉素类和超广谱头孢菌素具有广泛的活性,但对氨曲南无活性。GIM-1 给感染控制带来了巨大挑战,尤其是在根除革兰氏阴性病原体方面,包括肠杆菌科细菌、铜绿假单胞菌、鲍曼不动杆菌和非发酵菌。目前针对这些病原体处于后期研发阶段的药物很少或几乎没有,而 GIM-1 是开发针对产生 MBLs 的病原体的抗菌剂的潜在靶点。在本研究中,GIM-1 被克隆、过量表达并结晶。GIM-1 晶体的衍射分辨率达到 1.4 Å,属于正交晶系空间群 P2(1)2(1)2(1),晶胞参数 a = 38.5、b = 67.6、c = 72.8 Å。不对称单元中存在一个分子,相应的 V(M) 为 1.69 Å(3) Da(-1),溶剂含量为 27.1%。