Lecoq Lauriane, Bougault Catherine, Triboulet Sébastien, Dubée Vincent, Hugonnet Jean-Emmanuel, Arthur Michel, Simorre Jean-Pierre
Institut de Biologie Structurale Jean-Pierre Ebel, CEA, 41 rue Jules Horowitz, 38027, Grenoble, France.
Biomol NMR Assign. 2014 Oct;8(2):339-43. doi: 10.1007/s12104-013-9513-3. Epub 2013 Aug 2.
Penicillin-binding proteins were long considered as the only peptidoglycan cross-linking enzymes and one of the main targets of β-lactam antibiotics. A new class of transpeptidases, the L,D-transpeptidases, has emerged in the last decade. In most Gram-negative and Gram-positive bacteria, these enzymes generally have nonessential roles in peptidoglycan synthesis. In some clostridiae and mycobacteria, such as Mycobacterium tuberculosis, they are nevertheless responsible for the major peptidoglycan cross-linking pathway. L,D-Transpeptidases are thus considered as appealing new targets for the development of innovative therapeutic approaches. Carbapenems are currently investigated in this perspective as they are active on extensively drug-resistant M. tuberculosis and represent the only β-lactam class inhibiting L,D-transpeptidases. The molecular basis of the enzyme selectivity for carbapenems nevertheless remains an open question. Here we present the backbone and side-chain (1)H, (13)C, (15)N NMR assignments of the catalytic domain of Enterococcus faecium L,D-transpeptidase before and after acylation with the carbapenem ertapenem, as a prerequisite for further structural and functional studies.
青霉素结合蛋白长期以来被认为是唯一的肽聚糖交联酶，也是β-内酰胺类抗生素的主要靶点之一。在过去十年中，一类新的转肽酶——L,D-转肽酶出现了。在大多数革兰氏阴性菌和革兰氏阳性菌中，这些酶在肽聚糖合成中通常发挥非必需作用。然而，在一些梭菌属和分枝杆菌属细菌中，如结核分枝杆菌，它们却是主要肽聚糖交联途径的关键因素。因此，L,D-转肽酶被视为开发创新治疗方法的有吸引力的新靶点。鉴于碳青霉烯类药物对广泛耐药的结核分枝杆菌具有活性，且是唯一能抑制L,D-转肽酶的β-内酰胺类药物，目前正从这一角度对其进行研究。然而，该酶对碳青霉烯类药物选择性的分子基础仍是一个悬而未决的问题。在此，我们给出了粪肠球菌L,D-转肽酶催化结构域在被碳青霉烯类药物厄他培南酰化前后的主链和侧链（1）H、（13）C、（15）N NMR归属，这是进一步开展结构和功能研究的前提条件。
