Frère Jean-Marie, Page Malcolm G P
CIP, Institut de Chimie, B6a Sart-Tilman, B-4000 Liège, Belgium.
Basilea Pharmaceutica International Ltd, Grenzacherstr. 487, CH-4058 Basel, Switzerland.
Curr Opin Pharmacol. 2014 Oct;18:112-9. doi: 10.1016/j.coph.2014.09.012. Epub 2014 Oct 14.
The penicillin-binding proteins (PBPs) are well known targets for the β-lactam antibiotics. They continue to be a focus of interest for pharmaceutical design, as exemplified by the number of new agents under clinical investigation as well as novel experimental molecules. Considerable advances have been made in understanding the structure and function of this family of enzymes, through high-resolution structural studies and mechanistic studies in solution. These studies have thrown light on role of the high molecular mass PBPs in mediating β-lactam resistance, although much work remains to be done to enable a full description of the mechanisms by which these proteins modulate their sensitivity towards β-lactams while retaining their essential activity in cell wall biosynthesis.
青霉素结合蛋白（PBPs）是β-内酰胺类抗生素广为人知的作用靶点。它们仍然是药物设计关注的焦点，临床研究中的新型药物数量以及新型实验分子就是例证。通过高分辨率结构研究和溶液中的机制研究，在理解这类酶的结构和功能方面已经取得了相当大的进展。这些研究揭示了高分子量PBPs在介导β-内酰胺耐药性中的作用，尽管要全面描述这些蛋白质调节其对β-内酰胺敏感性同时在细胞壁生物合成中保持其基本活性的机制，仍有许多工作要做。
