金属β-内酰胺酶GOB是一种具有新型活性位点的单锌（II）酶。
The metallo-beta-lactamase GOB is a mono-Zn(II) enzyme with a novel active site.
作者信息
Morán-Barrio Jorgelina, González Javier M, Lisa María Natalia, Costello Alison L, Peraro Matteo Dal, Carloni Paolo, Bennett Brian, Tierney David L, Limansky Adriana S, Viale Alejandro M, Vila Alejandro J
机构信息
Departamento de Química Biológica and Departamento de Microbiología, Instituto de Biología Molecular y Celular de Rosario (IBR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina.
Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131.
出版信息
J Biol Chem. 2007 Jun 22;282(25):18286-18293. doi: 10.1074/jbc.M700467200. Epub 2007 Apr 2.
Metallo-beta-lactamases (MbetaLs) are zinc-dependent enzymes able to hydrolyze and inactivate most beta-lactam antibiotics. The large diversity of active site structures and metal content among MbetaLs from different sources has limited the design of a pan-MbetaL inhibitor. Here we report the biochemical and biophysical characterization of a novel MbetaL, GOB-18, from a clinical isolate of a Gram-negative opportunistic pathogen, Elizabethkingia meningoseptica. Different spectroscopic techniques, three-dimensional modeling, and mutagenesis experiments, reveal that the Zn(II) ion is bound to Asp120, His121, His263, and a solvent molecule, i.e. in the canonical Zn2 site of dinuclear MbetaLs. Contrasting all other related MbetaLs, GOB-18 is fully active against a broad range of beta-lactam substrates using a single Zn(II) ion in this site. These data further enlarge the structural diversity of MbetaLs.
金属β-内酰胺酶（MbetaLs）是一类依赖锌的酶，能够水解并使大多数β-内酰胺抗生素失活。不同来源的MbetaLs活性位点结构和金属含量差异很大，这限制了泛MbetaL抑制剂的设计。在此，我们报告了一种新型MbetaL——GOB-18的生化和生物物理特性，该酶来自革兰氏阴性机会致病菌脑膜败血伊丽莎白金菌的临床分离株。不同的光谱技术、三维建模和诱变实验表明，Zn（II）离子与Asp120、His121、His263以及一个溶剂分子结合，即在双核MbetaLs的典型Zn2位点。与所有其他相关MbetaLs不同的是，GOB-18在该位点使用单个Zn（II）离子就能对多种β-内酰胺底物具有完全活性。这些数据进一步扩大了MbetaLs的结构多样性。
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