Docquier Jean Denis, Benvenuti Manuela, Calderone Vito, Rossolini Gian Maria, Mangani Stefano
Dipartimento di Biologia Molecolare, Laboratorio di Fisiologia e Biotecnologia dei Microrganismi, Università di Siena, I-53100 Siena, Italy.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Mar 1;67(Pt 3):303-6. doi: 10.1107/S1744309110054680. Epub 2011 Feb 18.
TEM-72, a class A β-lactamase identified in isolates of Enterobacteriaceae, is a quadruple mutant of TEM-1 (Q39K, M182T, G238S and E240K) and shows extended-spectrum β-lactamase (ESBL) properties arising from the G238S and E240K substitutions. Although many structures of TEM variants have been published, they do not include an enzyme with the simultaneous presence of both of the ESBL-conferring G238S and E240K substitutions. Furthermore, the structure shows the presence of a citrate anion bound to the TEM-72 active site, where it interacts with all of the conserved residues of class A β-lactamases. The present structure supports the use of polycarboxylates as a scaffold for the design of broad-spectrum inhibitors of serine β-lactamases.
TEM-72是在肠杆菌科分离株中鉴定出的一种A类β-内酰胺酶，是TEM-1的四重突变体（Q39K、M182T、G238S和E240K），具有由G238S和E240K取代产生的超广谱β-内酰胺酶（ESBL）特性。尽管已发表了许多TEM变体的结构，但其中不包括同时存在赋予ESBL的G238S和E240K取代的酶。此外，该结构显示有一个柠檬酸根阴离子结合在TEM-72活性位点，在那里它与A类β-内酰胺酶的所有保守残基相互作用。目前的结构支持使用多羧酸盐作为设计丝氨酸β-内酰胺酶广谱抑制剂的支架。
