Spratt B G, Cromie K D
Microbial Genetics Group, School of Biological Sciences, University of Sussex, Brighton, United Kingdom.
Rev Infect Dis. 1988 Jul-Aug;10(4):699-711. doi: 10.1093/clinids/10.4.699.
beta-Lactam antibiotics exert their antibacterial effects by inactivating the high-molecular-weight penicillin-binding proteins (PBPs) that are responsible for the final stages of peptidoglycan biosynthesis. The availability of the amino acid sequences of several low-molecular-weight PBPs, high-molecular-weight PBPs, and active-site serine beta-lactamases has provided evidence that these groups of enzymes have a common, but distant, evolutionary origin. This view is strongly supported by the recent finding of a similarity in the three-dimensional structures of a low-molecular-weight PBP and class A beta-lactamases. The high-molecular-weight PBPs of Escherichia coli are believed to possess an amino-terminal peptidoglycan transglycosylase domain and a carboxy-terminal penicillin-sensitive transpeptidase domain. These enzymes are inserted in the cytoplasmic membrane only at their amino termini, and water-soluble forms have been obtained that should be suitable for crystallization and X-ray analysis. Resistance to beta-lactam antibiotics mediated by alterations of PBPs has been reported in some gram-negative bacteria. In isolates of Neisseria gonorrhoeae with chromosomally mediated resistance, penicillin-resistant PBPs have arisen from the introduction of multiple amino acid substitutions within the transpeptidase domain of the enzymes.
β-内酰胺类抗生素通过使负责肽聚糖生物合成最后阶段的高分子量青霉素结合蛋白（PBPs）失活来发挥其抗菌作用。几种低分子量PBPs、高分子量PBPs和活性位点丝氨酸β-内酰胺酶的氨基酸序列的可得性提供了证据，表明这些酶类具有共同但遥远的进化起源。低分子量PBP和A类β-内酰胺酶三维结构相似性的最近发现有力地支持了这一观点。大肠杆菌的高分子量PBPs被认为具有一个氨基末端肽聚糖转糖基酶结构域和一个羧基末端青霉素敏感转肽酶结构域。这些酶仅在其氨基末端插入细胞质膜，并且已经获得了应该适合结晶和X射线分析的水溶性形式。在一些革兰氏阴性细菌中已经报道了由PBPs改变介导的对β-内酰胺类抗生素的耐药性。在具有染色体介导耐药性的淋病奈瑟菌分离株中，耐青霉素的PBPs是由于在酶的转肽酶结构域内引入多个氨基酸取代而产生的。
