Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes.

INTRODUCTION ........................................................ 291 General ............... ......................................... 291 Cell Waill Structure and Synthesis ....................... ........................ 292 Identification of the Target of Penicillin Action .......... ........................ 293 PENICILLIN-BINDING COMPONENTS .............. .......................... 296 What Is Actually Bound? ....................................................... 298 How Much Penicillin Do Cells Bind? ................. ........................... 298 Is the Penicillin Bound Covalently? ................... .......................... 299 To What Group Does PenicillinBind?..... 299 Under What Conditions Can Penicillin Be Released from the PBCs?........ ........ 300 What Is the Physical Nature ofthe PBCs? ............. .......................... 300 Are PBCs Located in Peripheral Membranes, Mesosomes, or Both? ...... ........ 301 Do Organisms Have One or Multiple Proteins Which Bind Penicillin? ..... ...... 301 Isolation ofPBCs by Covalent Affinity Chromatography ........ ................. 303 What Is the Relationship of the PBCs to the Killing Site? ....... ................. 304 Biochemical Evidence for the Involvement ofPBCs in Peptidoglycan Synthesis . . 305 PENICILLIN-SENSITIVE ENZYMES ................ ........................... 306 Transpeptidase......................................................... 306 Transpeptidase assayed with natural acceptor in a coupled system ............ 306 Transpeptidase assayed with unnatural acceptor in a coupled system ..... ..... 307 Transpeptidase assayed in a simple, uncoupled system ....... ................. 307 D-Alanine Carboxypeptidase .................................................... 308 E. coli carboxypeptidase ...................................................... 309 Carboxypeptidases from Bacillus ................... .......................... 309 Streptomyces carboxypeptidases .................... .......................... 309 Endopeptidase......................................................... 313 Other Activities ........................................................ 314 Number of Enzymes Corresponding to the Different Penicillin-Sensitive Enzymatic Activities ........................................................ 314 Relationship ofthe Penicillin-Sensitive Enzymes to the PBCs ....... ............. 316 Physiological Functions ofthe Penicillin-Sensitive Enzymes ....... .............. 316 Physiological Evidence for the Existence of Multiple Transpeptidases ..... ...... 318 Kinetics of Penicillin Inhibition ................................................. 319 Models for the Interaction ofPenicillin with Its Target ........ .................. 321 MECHANISM OF KILLING BY PENICILLINS .......... ....................... 324 Mutant Analysis........................................................ 324 Evidence That Penicillin Kills by Inhibiting Cross-Linking ...................... 324 Killing by Amidino Penicillin ................................................... 325 Transfer of Penicillin Side Chain ................................................. 325 CONTROL OF CELL WALL SYNTHESIS ............. .......................... 326 SUMMARY ................ ....................................... 327 LITERATURE CITED ....................................................... 327