605:
410:
593:
31:
474:
ranging in molecular weight from 40,000 to 91,000. The different PBPs occur in different numbers per cell and have varied affinities for penicillin. The PBPs are usually broadly classified into high-molecular-weight (HMW) and low-molecular-weight (LMW) categories. Proteins that have evolved from PBPs
491:, which is the major component of bacterial cell walls. Bacterial cell wall synthesis is essential to growth, cell division (thus reproduction) and maintaining the cellular structure in bacteria. Inhibition of PBPs leads to defects in cell wall structure and irregularities in cell shape, for example
550:
antibiotics because they are similar in chemical structure to the modular pieces that form the peptidoglycan. When they bind to penicillin, the β-lactam amide bond is ruptured to form a covalent bond with the catalytic serine residue at the PBPs active site. This is an irreversible reaction and
559:
production). These experiments change the structure of PBP by adding different amino acids into the protein, allowing for new discovery of how the drug interacts with the protein. Research on PBPs has led to the discovery of new semi-synthetic β-lactams, wherein altering the side-chains on the
554:
There has been a great deal of research into PBPs because of their role in antibiotics and resistance. Bacterial cell wall synthesis and the role of PBPs in its synthesis is a very good target for drugs of selective toxicity because the metabolic pathways and enzymes are unique to bacteria.
537:
cytoskeleton and follow its rotation around the cell, inserting petipdoglycan in an oriented manner during cell growth. In contrast, high-molecular-weight PBPs are independent from MreB and maintain cell wall integrity by detecting and repairing defects in the peptidoglycan.
522:-alanine carboxypeptidase, peptidoglycan transpeptidase, and peptidoglycan endopeptidase. In all bacteria that have been studied, enzymes have been shown to catalyze more than one of the above reactions. The enzyme has a penicillin-insensitive transglycosylase
467:
There are a large number of PBPs, usually several in each organism, and they are found as both membrane-bound and cytoplasmic proteins. For example, Spratt (1977) reports that six different PBPs are routinely detected in all strains of
1030:
Vigouroux, Antoine; Cordier, Baptiste; Aristov, Andrey; Alvarez, Laura; Ă–zbaykal, Gizem; Chaze, Thibault; Oldewurtel, Enno Rainer; Matondo, Mariette; Cava, Felipe; Bikard, David; van
Teeffelen, Sven (2020-01-06).
413:
PBPs normally catalyze the cross-linking of the bacterial cell wall, but they can be permanently inhibited by penicillin and other β-lactam antibiotics. (NAM = N-acetylmuramic acid; NAG = N-acetylglucosamine)
506:
PBPs have been shown to catalyze a number of reactions involved in the process of synthesizing cross-linked peptidoglycan from lipid intermediates and mediating the removal of
604:
973:
Dion, Michael F.; Kapoor, Mrinal; Sun, Yingjie; Wilson, Sean; Ryan, Joel; Vigouroux, Antoine; Teeffelen, Sven van; Oldenbourg, Rudolf; Garner, Ethan C. (2019-05-13).
268:
159:
555:
Resistance to antibiotics has come about through overproduction of PBPs and formation of PBPs that have low affinity for penicillins (among other mechanisms such as
560:
original penicillin molecule has increased the affinity of PBPs for penicillin, and, thus, increased effectiveness in bacteria with developing resistance.
1310:
103:
91:
698:
Miyachiro MM, Contreras-Martel C, Dessen A (January 2020). "Penicillin-Binding
Proteins (PBPS) and Bacterial Cell Wall Elongation Complexes".
530:
domain (involved in cross-linking of the peptide subunits) and the serine at the active site is conserved in all members of the PBP family.
572:
17:
853:"Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy"
715:
288:
179:
1262:
851:
Peitsaro N, Polianskyte Z, Tuimala J, Pörn-Ares I, Liobikas J, Speer O, Lindholm D, Thompson J, Eriksson O (January 2008).
1304:
975:"Bacillus subtilis cell diameter is determined by the opposing actions of two distinct cell wall synthetic systems"
907:"Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action"
952:
276:
167:
564:
34:
Ribbon representation of the atomic structure of
Penicillin Binding Protein 3 from Pseudomonas aeruginosa
1337:
1284:
272:
163:
568:
1033:"Class-A penicillin binding proteins do not contribute to cell shape but repair cell-wall defects"
526:
domain (involved in formation of linear glycan strands) and a penicillin-sensitive transpeptidase
441:
642:
Sainsbury S, Bird L, Rao V, Shepherd SM, Stuart DI, Hunter WN, Owens RJ, Ren J (January 2011).
437:
547:
1096:
strain K15 in the form of a penicillin-sensitive D-alanyl-D-alanine-cleaving transpeptidase"
592:
445:
255:
146:
8:
115:
1296:
1120:
1091:
1067:
1032:
1007:
974:
944:
879:
852:
772:
751:
729:
672:
643:
96:
1222:
1185:
828:
799:
1300:
1254:
1227:
1166:
1125:
1072:
1054:
1012:
994:
936:
884:
833:
819:
777:
733:
721:
711:
677:
453:
391:
381:
371:
361:
351:
341:
331:
321:
311:
301:
295:
263:
154:
35:
1213:
217:
72:
1292:
1217:
1209:
1156:
1115:
1107:
1062:
1044:
1002:
986:
948:
926:
918:
874:
864:
823:
815:
767:
703:
667:
659:
470:
251:
142:
613:(top right of electron micrograph) occurs in some bacteria when PBP3 is inhibited.
120:
108:
1145:"Penicillin-binding protein-mediated resistance in pneumococci and staphylococci"
229:
84:
1246:
800:"Purification and partial characterization of a penicillin-binding protein from
707:
527:
523:
990:
922:
663:
1331:
1058:
998:
610:
492:
488:
1258:
1170:
1076:
1016:
940:
888:
869:
725:
681:
623:
452:
synthesis. PBPs are members of a subgroup of transpeptidase enzymes called
1231:
1129:
837:
436:; the name just reflects the way by which the protein was discovered. All
1092:"Isolation of the membrane-bound 26 000-Mr penicillin-binding protein of
781:
496:
1049:
409:
429:
1111:
931:
395:
385:
375:
365:
355:
345:
335:
325:
315:
305:
581:
The β-lactam ring is a structure common to all β-lactam antibiotics.
556:
449:
1276:
1161:
1144:
906:
850:
433:
224:
79:
1089:
797:
511:
425:
1183:
697:
515:
283:
174:
1090:
Nguyen-Distèche M, Leyh-Bouille M, Ghuysen JM (October 1982).
1029:
487:
PBPs are all involved in the final stages of the synthesis of
798:
Basu J, Chattopadhyay R, Kundu M, Chakrabarti P (July 1992).
500:
476:
39:
702:. Subcellular Biochemistry. Vol. 93. pp. 273–289.
428:
that are characterized by their affinity for and binding of
30:
700:
Macromolecular
Protein Complexes II: Structure and Function
534:
245:
212:
136:
67:
1184:
Ubukata K, Nonoguchi R, Matsuhashi M, Konno M (May 1989).
904:
644:"Crystal structures of penicillin-binding protein 3 from
475:
occur in many higher organisms and include the mammalian
641:
518:
have been shown to catalyze the following reactions:
1282:
905:
Cushnie TP, O'Driscoll NH, Lamb AJ (December 2016).
972:
1283:Bardal SK, Waechter JE, Martin DS (January 2011).
752:"Properties of the penicillin-binding proteins of
648:: comparison of native and antibiotic-bound forms"
533:Some low-molecular-weight PBPs associate with the
448:) bind to PBPs, which are essential for bacterial
1329:
495:, pseudomulticellular forms, lesions leading to
194:Penicillin-binding protein, dimerisation domain
1244:
514:from the precursor of peptidoglycan. Purified
793:
791:
1194:gene, which encodes a methicillin-resistant
1136:
745:
743:
1142:
900:
898:
844:
693:
691:
635:
1083:
788:
49:Penicillin-binding protein, transpeptidase
1238:
1221:
1160:
1119:
1066:
1048:
1006:
930:
878:
868:
827:
771:
749:
740:
671:
895:
688:
432:. They are a normal constituent of many
408:
29:
499:formation, and eventual cell death and
14:
1330:
1198:-specific penicillin-binding protein"
911:Cellular and Molecular Life Sciences
1245:Pandey N, Cascella M (March 2020).
24:
1297:10.1016/B978-1-4377-0310-8.00018-X
1285:"Chapter 18 - Infectious Diseases"
773:10.1111/j.1432-1033.1977.tb11258.x
25:
1349:
1186:"Expression and inducibility in
820:10.1128/jb.174.14.4829-4832.1992
760:European Journal of Biochemistry
603:
591:
1313:from the original on 2020-07-05
1265:from the original on 2020-12-15
1214:10.1128/jb.171.5.2882-2885.1989
1177:
955:from the original on 2017-10-07
584:
567:(PBP2A) is responsible for the
1149:Journal of Infectious Diseases
1023:
966:
541:
13:
1:
628:
565:penicillin binding protein 2A
240:Available protein structures:
131:Available protein structures:
652:Journal of Molecular Biology
462:
7:
708:10.1007/978-3-030-28151-9_8
618:
482:
418:Penicillin-binding proteins
18:Penicillin binding proteins
10:
1354:
1143:Chambers HF (March 1999).
1043:. Jie Xiao (ed.): –51998.
750:Spratt BG (January 1977).
1247:"Beta Lactam Antibiotics"
991:10.1038/s41564-019-0439-0
923:10.1007/s00018-016-2302-2
664:10.1016/j.jmb.2010.10.024
294:
282:
262:
244:
239:
235:
223:
211:
203:
198:
193:
173:
153:
135:
130:
126:
114:
102:
90:
78:
66:
58:
53:
48:
857:BMC Evolutionary Biology
563:Presence of the protein
551:inactivates the enzyme.
1202:Journal of Bacteriology
808:Journal of Bacteriology
802:Mycobacterium smegmatis
870:10.1186/1471-2148-8-26
646:Pseudomonas aeruginosa
573:methicillin-resistant
414:
43:
1188:Staphylococcus aureus
575:Staphylococcus aureus
569:antibiotic resistance
412:
38:, image created with
33:
1289:Applied Pharmacology
446:glutamine synthetase
442:tabtoxinine-β-lactam
438:β-lactam antibiotics
1155:(Suppl 2): S353-9.
1100:Biochemical Journal
1050:10.7554/eLife.51998
979:Nature Microbiology
1338:Bacterial proteins
424:s) are a group of
415:
44:
1112:10.1042/bj2070109
917:(23): 4471–4492.
717:978-3-030-28150-2
521:
509:
456:
444:, which inhibits
407:
406:
403:
402:
289:structure summary
189:
188:
185:
184:
180:structure summary
27:Class of proteins
16:(Redirected from
1345:
1322:
1321:
1319:
1318:
1280:
1274:
1273:
1271:
1270:
1242:
1236:
1235:
1225:
1181:
1175:
1174:
1164:
1140:
1134:
1133:
1123:
1087:
1081:
1080:
1070:
1052:
1027:
1021:
1020:
1010:
985:(8): 1294–1305.
970:
964:
963:
961:
960:
934:
902:
893:
892:
882:
872:
848:
842:
841:
831:
795:
786:
785:
775:
754:Escherichia coli
747:
738:
737:
695:
686:
685:
675:
639:
607:
598:Penicillin core.
595:
519:
507:
457:-transpeptidases
454:
398:
388:
378:
368:
358:
348:
338:
328:
318:
308:
237:
236:
191:
190:
128:
127:
46:
45:
21:
1353:
1352:
1348:
1347:
1346:
1344:
1343:
1342:
1328:
1327:
1326:
1325:
1316:
1314:
1307:
1281:
1277:
1268:
1266:
1243:
1239:
1182:
1178:
1141:
1137:
1088:
1084:
1028:
1024:
971:
967:
958:
956:
903:
896:
849:
845:
814:(14): 4829–32.
796:
789:
748:
741:
718:
696:
689:
640:
636:
631:
621:
614:
608:
599:
596:
587:
544:
485:
465:
390:
380:
370:
360:
350:
340:
330:
320:
310:
300:
92:OPM superfamily
28:
23:
22:
15:
12:
11:
5:
1351:
1341:
1340:
1324:
1323:
1305:
1275:
1237:
1176:
1162:10.1086/513854
1135:
1082:
1022:
965:
894:
843:
787:
739:
716:
687:
633:
632:
630:
627:
620:
617:
616:
615:
609:
602:
600:
597:
590:
586:
583:
543:
540:
484:
481:
464:
461:
405:
404:
401:
400:
298:
292:
291:
286:
280:
279:
266:
260:
259:
249:
242:
241:
233:
232:
227:
221:
220:
215:
209:
208:
205:
201:
200:
196:
195:
187:
186:
183:
182:
177:
171:
170:
157:
151:
150:
140:
133:
132:
124:
123:
118:
112:
111:
106:
100:
99:
94:
88:
87:
82:
76:
75:
70:
64:
63:
60:
56:
55:
51:
50:
26:
9:
6:
4:
3:
2:
1350:
1339:
1336:
1335:
1333:
1312:
1308:
1306:9781437703108
1302:
1298:
1294:
1290:
1286:
1279:
1264:
1260:
1256:
1252:
1248:
1241:
1233:
1229:
1224:
1219:
1215:
1211:
1208:(5): 2882–5.
1207:
1203:
1199:
1197:
1193:
1189:
1180:
1172:
1168:
1163:
1158:
1154:
1150:
1146:
1139:
1131:
1127:
1122:
1117:
1113:
1109:
1106:(1): 109–15.
1105:
1101:
1097:
1095:
1086:
1078:
1074:
1069:
1064:
1060:
1056:
1051:
1046:
1042:
1038:
1034:
1026:
1018:
1014:
1009:
1004:
1000:
996:
992:
988:
984:
980:
976:
969:
954:
950:
946:
942:
938:
933:
928:
924:
920:
916:
912:
908:
901:
899:
890:
886:
881:
876:
871:
866:
862:
858:
854:
847:
839:
835:
830:
825:
821:
817:
813:
809:
805:
803:
794:
792:
783:
779:
774:
769:
766:(2): 341–52.
765:
761:
757:
755:
746:
744:
735:
731:
727:
723:
719:
713:
709:
705:
701:
694:
692:
683:
679:
674:
669:
665:
661:
658:(1): 173–84.
657:
653:
649:
647:
638:
634:
626:
625:
612:
611:Filamentation
606:
601:
594:
589:
588:
582:
579:
577:
576:
570:
566:
561:
558:
552:
549:
546:PBPs bind to
539:
536:
531:
529:
525:
517:
513:
504:
502:
498:
494:
493:filamentation
490:
489:peptidoglycan
480:
478:
473:
472:
460:
458:
451:
447:
443:
439:
435:
431:
427:
423:
419:
411:
397:
393:
387:
383:
377:
373:
367:
363:
357:
353:
347:
343:
337:
333:
327:
323:
317:
313:
307:
303:
299:
297:
293:
290:
287:
285:
281:
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261:
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206:
202:
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192:
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178:
176:
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169:
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158:
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148:
144:
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138:
134:
129:
125:
122:
119:
117:
113:
110:
107:
105:
101:
98:
95:
93:
89:
86:
83:
81:
77:
74:
71:
69:
65:
61:
57:
52:
47:
41:
37:
32:
19:
1315:. Retrieved
1288:
1278:
1267:. Retrieved
1250:
1240:
1205:
1201:
1195:
1191:
1187:
1179:
1152:
1148:
1138:
1103:
1099:
1094:Streptomyces
1093:
1085:
1040:
1036:
1025:
982:
978:
968:
957:. Retrieved
914:
910:
860:
856:
846:
811:
807:
801:
763:
759:
753:
699:
655:
651:
645:
637:
624:PASTA domain
622:
585:Other images
580:
574:
562:
553:
545:
532:
505:
486:
469:
466:
440:(except for
421:
417:
416:
62:PCN-bd_Tpept
1291:: 233–291.
542:Antibiotics
497:spheroplast
199:Identifiers
104:OPM protein
54:Identifiers
1317:2020-05-01
1269:2020-05-01
1251:StatPearls
959:2020-05-01
932:10059/2129
629:References
528:C-terminal
524:N-terminal
430:penicillin
252:structures
143:structures
116:Membranome
36:(PDB 3OC2)
1196:S. aureus
1059:2050-084X
999:2058-5276
734:210814189
557:lactamase
479:protein.
463:Diversity
450:cell wall
230:IPR005311
207:PBP_dimer
85:IPR001460
1332:Category
1311:Archived
1263:Archived
1259:31424895
1171:10081507
1077:31904338
1017:31086310
953:Archived
941:27392605
889:18226203
726:31939154
682:20974151
619:See also
578:(MRSA).
571:seen in
548:β-lactam
483:Function
434:bacteria
426:proteins
389:
379:
369:
359:
349:
339:
329:
319:
309:
269:RCSB PDB
225:InterPro
160:RCSB PDB
80:InterPro
1232:2708325
1190:of the
1130:7181854
1121:1153830
1068:7002073
1008:6656618
949:2065821
880:2266909
838:1624470
673:3025346
516:enzymes
512:alanine
471:E. coli
399:
218:PF03717
73:PF00905
1303:
1257:
1230:
1223:209980
1220:
1169:
1128:
1118:
1075:
1065:
1057:
1015:
1005:
997:
947:
939:
887:
877:
863:: 16.
836:
829:206282
826:
782:319999
780:
732:
724:
714:
680:
670:
284:PDBsum
258:
248:
204:Symbol
175:PDBsum
149:
139:
59:Symbol
1037:eLife
945:S2CID
756:K12,"
730:S2CID
501:lysis
477:LACTB
40:PyMol
1301:ISBN
1255:PMID
1228:PMID
1192:mecA
1167:PMID
1126:PMID
1073:PMID
1055:ISSN
1013:PMID
995:ISSN
937:PMID
885:PMID
834:PMID
778:PMID
722:PMID
712:ISBN
678:PMID
535:MreB
396:1rp5
386:1qmf
376:1qme
366:1pyy
356:1pmd
346:1mwu
336:1mwt
326:1mws
316:1mwr
306:1k25
277:PDBj
273:PDBe
256:ECOD
246:Pfam
213:Pfam
168:PDBj
164:PDBe
147:ECOD
137:Pfam
109:5hlb
68:Pfam
1293:doi
1218:PMC
1210:doi
1206:171
1157:doi
1153:179
1116:PMC
1108:doi
1104:207
1063:PMC
1045:doi
1003:PMC
987:doi
927:hdl
919:doi
875:PMC
865:doi
824:PMC
816:doi
812:174
768:doi
704:doi
668:PMC
660:doi
656:405
422:PBP
392:PDB
382:PDB
372:PDB
362:PDB
352:PDB
342:PDB
332:PDB
322:PDB
312:PDB
302:PDB
296:PDB
264:PDB
155:PDB
121:541
97:195
1334::
1309:.
1299:.
1287:.
1261:.
1253:.
1249:.
1226:.
1216:.
1204:.
1200:.
1165:.
1151:.
1147:.
1124:.
1114:.
1102:.
1098:.
1071:.
1061:.
1053:.
1039:.
1035:.
1011:.
1001:.
993:.
981:.
977:.
951:.
943:.
935:.
925:.
915:73
913:.
909:.
897:^
883:.
873:.
859:.
855:.
832:.
822:.
810:.
806:.
790:^
776:.
764:72
762:.
758:.
742:^
728:.
720:.
710:.
690:^
676:.
666:.
654:.
650:.
503:.
459:.
455:DD
394::
384::
374::
364::
354::
344::
334::
324::
314::
304::
275:;
271:;
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