The Penicillin-Binding Proteins: Structure and Role in Peptidoglycan Biosynthesis

[en] Penicillin-binding proteins (PBPs) have been scrutinized for over 40 years. Recent structural information on PBPs together with the ongoing long-term biochemical experimental investigations, and results from more recent techniques such as protein localization by green fluorescent protein-fusion immunofluorescence or double-hybrid assay, have brought our understanding of the last stages of the peptidoglycan biosynthesis to an outstanding level that allows a broad outlook on the properties of these enzymes. Details are emerging regarding the interaction between the peptidoglycan-synthesizing PBPs and the peptidoglycan, their mesh net-like product that surrounds and protects bacteria. This review focuses on the detailed structure of PBPs and their implication in peptidoglycan synthesis, maturation and recycling. An overview of the content in PBPs of some bacteria is provided with an emphasis on comparing the biochemical properties of homologous PBPs (orthologues) belonging to different bacteria.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Sauvage, Eric ^✱; Université de Liège - ULiège > Centre d'ingénierie des protéines

Kerff, Frédéric ^✱; Université de Liège - ULiège > Centre d'ingénierie des protéines

Terrak, Mohammed ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Ayala, J. A.

Charlier, Paulette ; Université de Liège - ULiège > Centre d'ingénierie des protéines

^✱ These authors have contributed equally to this work.

Language :

English

Title :

The Penicillin-Binding Proteins: Structure and Role in Peptidoglycan Biosynthesis

Publication date :

March 2008

Journal title :

FEMS Microbiology Reviews

ISSN :

0168-6445

eISSN :

1574-6976

Publisher :

Oxford University Press, United Kingdom

Volume :

Issue :

Pages :

234-58

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 22 June 2009

Statistics

Number of views

125 (24 by ULiège)

Number of downloads

5 (5 by ULiège)

More statistics

Scopus citations^®

922

Scopus citations^®
without self-citations

882

OpenCitations

886

Bibliography

Adediran SA, Zhang Z, Nukaga M, Palzkill T Pratt RF (2005) The d-methyl group in beta-lactamase evolution: evidence from the Y221G and GC1 mutants of the class C beta-lactamase of Enterobacter cloacae P99. Biochemistry 44 : 7543 7552.
Antignac A, Kriz P, Tzanakaki G, Alonso JM Taha MK (2001) Polymorphism of Neisseria meningitidis penA gene associated with reduced susceptibility to penicillin. J Antimicrob Chemother 47 : 285 296.
Arbeloa A, Segal H, Hugonnet JE et al 2004) Role of class A penicillin-binding proteins in PBP5-mediated beta-lactam resistance in Enterococcus faecalis. J Bacteriol 186 : 1221 1228.
Arthur M, Depardieu F, Snaith HA, Reynolds PE Courvalin P (1994) Contribution of VanY d,d-carboxypeptidase to glycopeptide resistance in Enterococcus faecalis by hydrolysis of peptidoglycan precursors. Antimicrob Agents Chemother 38 : 1899 1903.
Atrih A, Bacher G, Allmaier G, Williamson MP Foster SJ (1999) Analysis of peptidoglycan structure from vegetative cells of Bacillus subtilis 168 and role of PBP 5 in peptidoglycan maturation. J Bacteriol 181 : 3956 3966.
Ayala J, Quesada A, Vadillo S, Criado J Piriz S (2005) Penicillin-binding proteins of Bacteroides fragilis and their role in the resistance to imipenem of clinical isolates. J Med Microbiol 54 : 1055 1064.
Barbour AG (1981) Properties of penicillin-binding proteins in Neisseria gonorrhoeae. Antimicrob Agents Chemother 19 : 316 322.
Barreteau H, Blanot D, Boniface A, Gobec S, Kovač A Sova M (2008) Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiol Rev 32 : 168 207.
Barrett D, Leimkuhler C, Chen L, Walker D, Kahne D Walker S (2005) Kinetic characterization of the glycosyltransferase module of Staphylococcus aureus PBP2. J Bacteriol 187 : 2215 2217.
Barrett DS, Chen L, Litterman NK Walker S (2004) Expression and characterization of the isolated glycosyltransferase module of Escherichia coli PBP1b. Biochemistry 43 : 12375 12381.
Bertsche U, Breukink E, Kast T Vollmer W (2005) In vitro murein peptidoglycan synthesis by dimers of the bifunctional transglycosylase- transpeptidase PBP1B from Escherichia coli. J Biol Chem 280 : 38096 38101.
Bishop RE Weiner JH (1993) Complementation of growth defect in an ampC deletion mutant of Escherichia coli. FEMS Microbiol Lett 114 : 349 354.
Bompard-Gilles C, Remaut H, Villeret V et al 2000) Crystal structure of a d-aminopeptidase from Ochrobactrum anthropi, a new member of the 'penicillin-recognizing enzyme' family. Structure 8 : 971 980.
Born P, Breukink E Vollmer W (2006) In vitro synthesis of cross-linked murein and its attachment to sacculi by PBP1A from Escherichia coli. J Biol Chem 281 : 26985 26993.
Bouhss A, Trunkfield AE, Bugg TDH Mengin-Lecreulx D (2007) The biosynthesis of peptidoglycan lipid linked intermediates. FEMS Microbiol Rev 32 : 208 233.
Breukink E, van Heusden HE, Vollmerhaus PJ et al 2003) Lipid II is an intrinsic component of the pore induced by nisin in bacterial membranes. J Biol Chem 278 : 19898 19903.
Buchanan CE Sowell MO (1982) Synthesis of penicillin-binding protein 6 by stationary-phase Escherichia coli. J Bacteriol 151 : 491 494.
Casadewall B, Reynolds PE Courvalin P (2001) Regulation of expression of the vanD glycopeptide resistance gene cluster from Enterococcus faecium BM4339. J Bacteriol 183 : 3436 3446.
Chen L, Walker D, Sun B, Hu Y, Walker S Kahne D (2003) Vancomycin analogues active against vanA-resistant strains inhibit bacterial transglycosylase without binding substrate. Proc Natl Acad Sci USA 100 : 5658 5663.
Contreras-Martel C, Job V, Di Guilmi AM, Vernet T, Dideberg O Dessen A (2006) Crystal structure of penicillin-binding protein 1a (PBP1a) reveals a mutational hotspot implicated in beta-lactam resistance in Streptococcus pneumoniae. J Mol Biol 355 : 684 696.
Courvalin P (2006) Vancomycin resistance in gram-positive cocci. Clin Infect Dis 42 (Suppl 1) : S25 S34.
Daniel RA, Harry EJ Errington J (2000) Role of penicillin-binding protein PBP 2B in assembly and functioning of the division machinery of Bacillus subtilis. Mol Microbiol 35 : 299 311.
Dasgupta A, Datta P, Kundu M Basu J (2006) The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division. Microbiology 152 : 493 504.
Davies C, White SW Nicholas RA (2001) Crystal structure of a deacylation-defective mutant of penicillin-binding protein 5 at 2.3-A resolution. J Biol Chem 276 : 616 623.
Den Blaauwen T, Aarsman ME, Vischer NO Nanninga N (2003) Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. Mol Microbiol 47 : 539 547.
den Blaauwen T, de Pedro M, Nguyen-Distèche M Ayala J (2008) Morphogenesis of rod-shaped sacculi. FEMS Microbiol Rev 32 : 321 344.
Denome SA, Elf PK, Henderson TA, Nelson DE Young KD (1999) Escherichia coli mutants lacking all possible combinations of eight penicillin binding proteins: viability, characteristics, and implications for peptidoglycan synthesis. J Bacteriol 181 : 3981 3993.
Di Berardino M, Dijkstra A, Stuber D, Keck W Gubler M (1996) The monofunctional glycosyltransferase of Escherichia coli is a member of a new class of peptidoglycan-synthesising enzymes. FEBS Lett 392 : 184 188.
Di Guilmi AM, Mouz N, Andrieu JP et al 1998) Identification, purification, and characterization of transpeptidase and glycosyltransferase domains of Streptococcus pneumoniae penicillin-binding protein 1a. J Bacteriol 180 : 5652 5659.
Di Guilmi AM, Mouz N, Martin L, Hoskins J, Jaskunas SR, Dideberg O Vernet T (1999) Glycosyltransferase domain of penicillin-binding protein 2a from Streptococcus pneumoniae is membrane associated. J Bacteriol 181 : 2773 2781.
Di Guilmi AM, Dessen A, Dideberg O Vernet T (2003a) Functional characterization of penicillin-binding protein 1b from Streptococcus pneumoniae. J Bacteriol 185 : 1650 1658.
Di Guilmi AM, Dessen A, Dideberg O Vernet T (2003b) The glycosyltransferase domain of penicillin-binding protein 2a from Streptococcus pneumoniae catalyzes the polymerization of murein glycan chains. J Bacteriol 185 : 4418 4423.
Di Lallo G, Fagioli M, Barionovi D, Ghelardini P Paolozzi L (2003) Use of a two-hybrid assay to study the assembly of a complex multicomponent protein machinery: bacterial septosome differentiation. Microbiology 149 : 3353 3359.
Dive G Dehareng D (1999) Serine peptidase catalytic machinery: cooperative one-step mechanism. Int J Quant Chem 73 : 161 174.
Dougherty TJ, Koller AE Tomasz A (1980) Penicillin-binding proteins of penicillin-susceptible and intrinsically resistant Neisseria gonorrhoeae. Antimicrob Agents Chemother 18 : 730 737.
Dowson CG, Jephcott AE, Gough KR Spratt BG (1989) Penicillin-binding protein 2 genes of non-beta-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae. Mol Microbiol 3 : 35 41.
Duez C, Zorzi W, Sapunaric F, Amoroso A, Thamm I Coyette J (2001a) The penicillin resistance of Enterococcus faecalis JH2-2r results from an overproduction of the low-affinity penicillin-binding protein PBP4 and does not involve a psr-like gene. Microbiology 147 : 2561 2569.
Duez C, Vanhove M, Gallet X, Bouillenne F, Docquier J, Brans A Frère J (2001b) Purification and characterization of PBP4a, a new low-molecular-weight penicillin-binding protein from Bacillus subtilis. J Bacteriol 183 : 1595 1599.
el Kharroubi A, Piras G, Jacques P, Szabo I, Van Beeumen J, Coyette J Ghuysen JM (1989) Active-site and membrane topology of the dd-peptidase/ penicillin-binding protein no. 6 of Enterococcus hirae (Streptococcus faecium) A.T.C.C. 9790. Biochem J 262 : 457 462.
Fonzé E, Vermeire M, Nguyen-Distèche M, Brasseur R Charlier P (1999) The crystal structure of a penicilloyl-serine transferase of intermediate penicillin sensitivity. The dd-transpeptidase of Streptomyces K15. J Biol Chem 274 : 21853 21860.
Frère JM (2004) Streptomyces R61 d-Ala-d-Ala carboxypeptidase. Handbook of Proteolytic Enzymes. 2nd edn (Barrett AJ, Rawlings ND Woessner JF, eds), pp. 1959 1962. Elsevier, London.
Gallant CV, Daniels C, Leung JM, Ghosh AS, Young KD, Kotra LP Burrows LL (2005) Common beta-lactamases inhibit bacterial biofilm formation. Mol Microbiol 58 : 1012 1024.
Georgopapadakou NH, Smith SA Sykes RB (1982) Mode of action of azthreonam. Antimicrob Agents Chemother 21 : 950 956.
Ghosh AS Young KD (2003) Sequences near the active site in chimeric penicillin binding proteins 5 and 6 affect uniform morphology of Escherichia coli. J Bacteriol 185 : 2178 2186.
Ghuysen JM (1968) Use of bacteriolytic enzymes in determination of wall structure and their role in cell metabolism. Bacteriol Rev 32 : 425 464.
Ghuysen JM (1991) Serine beta-lactamases and penicillin-binding proteins. Annu Rev Microbiol 45 : 37 67.
Giesbrecht P, Wecke J Reinicke B (1976) On the morphogenesis of the cell wall of staphylococci. Int Rev Cytol 44 : 225 318.
Gittins JR, Phoenix DA Pratt JM (1994) Multiple mechanisms of membrane anchoring of Escherichia coli penicillin-binding proteins. FEMS Microbiol Rev 13 : 1 12.
Goffin C Ghuysen JM (1998) Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol Mol Biol Rev 62 : 1079 1093.
Goffin C Ghuysen JM (2002) Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent. Microbiol Mol Biol Rev 66 : 702 738, table of contents.
Gordon E, Mouz N, Duee E Dideberg O (2000) The crystal structure of the penicillin-binding protein 2x from Streptococcus pneumoniae and its acyl-enzyme form: implication in drug resistance. J Mol Biol 299 : 477 485.
Granier B, Duez C, Lepage S et al 1992) Primary and predicted secondary structures of the Actinomadura R39 extracellular dd-peptidase, a penicillin-binding protein (PBP) related to the Escherichia coli PBP4. Biochem J 282 (Part 3) : 781 788.
Guinane CM, Cotter PD, Ross RP Hill C (2006) Contribution of penicillin-binding protein homologs to antibiotic resistance, cell morphology, and virulence of Listeria monocytogenes EGDe. Antimicrob Agents Chemother 50 : 2824 2828.
Hakenbeck R (2000) Transformation in Streptococcus pneumoniae: mosaic genes and the regulation of competence. Res Microbiol 151 : 453 456.
Hara H Suzuki H (1984) A novel glycan polymerase that synthesizes uncross-linked peptidoglycan in Escherichia coli. FEBS Lett 168 : 155 160.
Harris F, Brandenburg K, Seydel U Phoenix D (2002) Investigations into the mechanisms used by the C-terminal anchors of Escherichia coli penicillin-binding proteins 4, 5, 6 and 6b for membrane interaction. Eur J Biochem 269 : 5821 5829.
Heller H, Schaefer M Schulten K (1993) Molecular dynamics simulation of a bilayer of 200 lipids in the gel and in the liquid-crystal phases. J Phys Chem 97 : 8343 8360.
Henderson TA, Young KD, Denome SA Elf PK (1997) AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli. J Bacteriol 179 : 6112 6121.
Höltje JV (1995) From growth to autolysis: the murein hydrolases in Escherichia coli. Arch Microbiol 164 : 243 254.
Höltje JV (1998) Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli. Microbiol Mol Biol Rev 62 : 181 203.
Hoskins J, Matsushima P, Mullen DL et al 1999) Gene disruption studies of penicillin-binding proteins 1a, 1b, and 2a in Streptococcus pneumoniae. J Bacteriol 181 : 6552 6555.
Hotomi M, Billal DS, Shimada J, Suzumoto M, Yamauchi K, Fujihara K Yamanaka N (2006) High prevalence of Streptococcus pneumoniae with mutations in pbp1a, pbp2x, and pbp2b genes of penicillin-binding proteins in the nasopharynx in children in Japan. ORL J Otorhinolaryngol Relat Spec 68 : 139 145.
Hujer AM, Kania M, Gerken T et al 2005) Structure-activity relationships of different beta-lactam antibiotics against a soluble form of Enterococcus faecium PBP5, a type II bacterial transpeptidase. Antimicrob Agents Chemother 49 : 612 618.
Jamin M, Adam M, Damblon C, Christiaens L Frere JM (1991) Accumulation of acyl-enzyme in dd-peptidase-catalysed reactions with analogues of peptide substrates. Biochem J 280 (Pt 2) : 499 506.
Judd RC, Strange JC, Pettit RK Shafer WM (1991) Identification and characterization of a conserved outer-membrane protein of Neisseria gonorrhoeae. Mol Microbiol 5 : 1091 1096.
Karimova G, Dautin N Ladant D (2005) Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis. J Bacteriol 187 : 2233 2243.
Kishida H, Unzai S, Roper DI, Lloyd A, Park SY Tame JR (2006) Crystal structure of penicillin binding protein 4 (dacB) from Escherichia coli, both in the native form and covalently linked to various antibiotics. Biochemistry 45 : 783 792.
Korat B, Mottl H Keck W (1991) Penicillin-binding protein 4 of Escherichia coli: molecular cloning of the dacB gene, controlled overexpression, and alterations in murein composition. Mol Microbiol 5 : 675 684.
Korsak D, Vollmer W Markiewicz Z (2005a) Listeria monocytogenes EGD lacking penicillin-binding protein 5 (PBP5) produces a thicker cell wall. FEMS Microbiol Lett 251 : 281 288.
Korsak D, Popowska M Markiewicz Z (2005b) Analysis of the murein of a Listeria monocytogenes EGD mutant lacking functional penicillin binding protein 5 (PBP5). Pol J Microbiol 54 : 339 342.
Kuzin AP, Liu H, Kelly JA Knox JR (1995) Binding of cephalothin and cefotaxime to d-ala-d-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. Biochemistry 34 : 9532 9540.
Kwon DH, Dore MP, Kim JJ, Kato M, Lee M, Wu JY Graham DY (2003) High-level beta-lactam resistance associated with acquired multidrug resistance in Helicobacter pylori. Antimicrob Agents Chemother 47 : 2169 2178.
Lawrence PJ Strominger JL (1970) Biosynthesis of the peptidoglycan of bacterial cell walls. XVI. The reversible fixation of radioactive penicillin G to the d-alanine carboxypeptidase of Bacillus subtilis. J Biol Chem 245 : 3660 3666.
Lazaro S, Fernandez-Pinas F, Fernandez-Valiente E, Blanco-Rivero A Leganes F (2001) pbpB, a gene coding for a putative penicillin-binding protein, is required for aerobic nitrogen fixation in the cyanobacterium Anabaena sp. strain PCC7120. J Bacteriol 183 : 628 636.
Lee J, Feldman AR, Delmas B Paetzel M (2007) Crystal structure of the VP4 protease from infectious pancreatic necrosis virus reveals the acyl-enzyme complex for an intermolecular self-cleavage reaction. J Biol Chem 282 : 24928 24937.
Leganes F, Blanco-Rivero A, Fernandez-Pinas F et al 2005) Wide variation in the cyanobacterial complement of presumptive penicillin-binding proteins. Arch Microbiol 184 : 234 248.
Leimanis S, Hoyez N, Hubert S, Laschet M, Sauvage E, Brasseur R Coyette J (2006) PBP5 complementation of a PBP3 deficiency in Enterococcus hirae. J Bacteriol 188 : 6298 6307.
Leski TA Tomasz A (2005) Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. J Bacteriol 187 : 1815 1824.
Lim D Strynadka NC (2002) Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat Struct Biol 9 : 870 876.
Liu H Wong CH (2006) Characterization of a transglycosylase domain of Streptococcus pneumoniae PBP1b. Bioorg Med Chem 14 : 7187 7195.
Lovering AL, De Castro L, Lim D Strynadka NC (2006) Structural analysis of an "open" form of PBP1B from Streptococcus pneumoniae. Protein Sci 15 : 1701 1709.
Lovering AL, de Castro LH, Lim D Strynadka NC (2007) Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis. Science 315 : 1402 1405.
Lu WP, Sun Y, Bauer MD, Paule S, Koenigs PM Kraft WG (1999) Penicillin-binding protein 2a from methicillin-resistant Staphylococcus aureus: kinetic characterization of its interactions with beta-lactams using electrospray mass spectrometry. Biochemistry 38 : 6537 6546.
Macheboeuf P, Di Guilmi AM, Job V, Vernet T, Dideberg O Dessen A (2005) Active site restructuring regulates ligand recognition in class A penicillin-binding proteins. Proc Natl Acad Sci USA 102 : 577 582.
Macheboeuf P, Contreras-Martel C, Job V, Dideberg O Dessen A (2006) Penicillin binding proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiol Rev 30 : 673 691.
Matsuhashi M, Tamaki S, Curtis SJ Strominger JL (1979) Mutational evidence for identity of penicillin-binding protein 5 in Escherichia coli with the major d-alanine carboxypeptidase IA activity. J Bacteriol 137 : 644 647.
McDonough MA, Anderson JW, Silvaggi NR, Pratt RF, Knox JR Kelly JA (2002) Structures of two kinetic intermediates reveal species specificity of penicillin-binding proteins. J Mol Biol 322 : 111 122.
McPherson DC Popham DL (2003) Peptidoglycan synthesis in the absence of class A penicillin-binding proteins in Bacillus subtilis. J Bacteriol 185 : 1423 1431.
Meberg BM, Sailer FC, Nelson DE Young KD (2001) Reconstruction of Escherichia coli mrcA (PBP 1a) mutants lacking multiple combinations of penicillin binding proteins. J Bacteriol 183 : 6148 6149.
Meberg BM, Paulson AL, Priyadarshini R Young KD (2004) Endopeptidase penicillin-binding proteins 4 and 7 play auxiliary roles in determining uniform morphology of Escherichia coli. J Bacteriol 186 : 8326 8336.
Mercer KL Weiss DS (2002) The Escherichia coli cell division protein FtsW is required to recruit its cognate transpeptidase, FtsI (PBP3), to the division site. J Bacteriol 184 : 904 912.
Meroueh SO, Bencze KZ, Hesek D, Lee M, Fisher JF, Stemmler TL Mobashery S (2006) Three-dimensional structure of the bacterial cell wall peptidoglycan. Proc Natl Acad Sci USA 103 : 4404 4409.
Morlot C, Noirclerc-Savoye M, Zapun A, Dideberg O Vernet T (2004) The d,d-carboxypeptidase PBP3 organizes the division process of Streptococcus pneumoniae. Mol Microbiol 51 : 1641 1648.
Morlot C, Pernot L, Le Gouellec A, Di Guilmi AM, Vernet T, Dideberg O Dessen A (2005) Crystal structure of a peptidoglycan synthesis regulatory factor (PBP3) from Streptococcus pneumoniae. J Biol Chem 280 : 15984 15991.
Morosini MI, Ayala JA, Baquero F, Martinez JL Blazquez J (2000) Biological cost of AmpC production for Salmonella enterica serotype Typhimurium. Antimicrob Agents Chemother 44 : 3137 3143.
Mottl H, Anderluzzi D, Kraft A Holtje J (1995) Towards the enzymology of the transglycosylase reaction: studies of the transglycosylase activity of the penicillin-binding protein 1a of Escherichia coli Abstracts of the symposium of the envelope in bacterial physiology and antibiotic action, Garda, Italy. p.70.
Murray T, Popham DL, Pearson CB, Hand AR Setlow P (1998) Analysis of outgrowth of Bacillus subtilis spores lacking penicillin-binding protein 2a. J Bacteriol 180 : 6493 6502.
Nelson DE Young KD (2000) Penicillin binding protein 5 affects cell diameter, contour, and morphology of Escherichia coli. J Bacteriol 182 : 1714 1721.
Nelson DE Young KD (2001) Contributions of PBP 5 and dd-carboxypeptidase penicillin binding proteins to maintenance of cell shape in Escherichia coli. J Bacteriol 183 : 3055 3064.
Nguyen-Disteche M, Leyh-Bouille M Ghuysen JM (1982) Isolation of the membrane-bound 26 000-Mr penicillin-binding protein of Streptomyces strain K15 in the form of a penicillin-sensitive d-alanyl-d-alanine-cleaving transpeptidase. Biochem J 207 : 109 115.
Nicholas RA, Krings S, Tomberg J, Nicola G Davies C (2003) Crystal structure of wild-type penicillin-binding protein 5 from Escherichia coli: implications for deacylation of the acyl-enzyme complex. J Biol Chem 278 : 52826 52833.
Nicola G, Peddi S, Stefanova M, Nicholas RA, Gutheil WG Davies C (2005) Crystal structure of Escherichia coli penicillin-binding protein 5 bound to a tripeptide boronic acid inhibitor: a role for Ser-110 in deacylation. Biochemistry 44 : 8207 8217.
Offant J, Michoux F, Dermiaux A, Biton J Bourne Y (2006) Functional characterization of the glycosyltransferase domain of penicillin-binding protein 1a from Thermotoga maritima. Biochim Biophys Acta 1764 : 1036 1042.
Okazaki S, Suzuki A, Komeda H, Yamaguchi S, Asano Y Yamane T (2007) Crystal structure and functional characterization of a d-stereospecific amino acid amidase from Ochrobactrum anthropi SV3, a new member of the penicillin-recognizing proteins. J Mol Biol 368 : 79 91.
Paetzel M Dalbey RE (1997) Catalytic hydroxyl/amine dyads within serine proteases. Trends Biochem Sci 22 : 28 31.
Palomeque-Messia P, Englebert S, Leyh-Bouille M et al 1991) Amino acid sequence of the penicillin-binding protein/dd-peptidase of Streptomyces K15. Predicted secondary structures of the low Mr penicillin-binding proteins of class A. Biochem J 279 (Part 1) : 223 230.
Pares S, Mouz N, Petillot Y, Hakenbeck R Dideberg O (1996) X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme. Nat Struct Biol 3 : 284 289.
Pereira SF, Henriques AO, Pinho MG, de Lencastre H Tomasz A (2007) Role of PBP1 in cell division of Staphylococcus aureus. J Bacteriol 189 : 3525 3531.
Piette A, Fraipont C, Den Blaauwen T, Aarsman ME, Pastoret S Nguyen-Disteche M (2004) Structural determinants required to target penicillin-binding protein 3 to the septum of Escherichia coli. J Bacteriol 186 : 6110 6117.
Pinho MG Errington J (2003) Dispersed mode of Staphylococcus aureus cell wall synthesis in the absence of the division machinery. Mol Microbiol 50 : 871 881.
Pinho MG Errington J (2005) Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates. Mol Microbiol 55 : 799 807.
Pinho MG, de Lencastre H Tomasz A (2000) Cloning, characterization, and inactivation of the gene pbpC, encoding penicillin-binding protein 3 of Staphylococcus aureus. J Bacteriol 182 : 1074 1079.
Popham DL Setlow P (1993) Cloning, nucleotide sequence, and regulation of the Bacillus subtilis pbpE operon, which codes for penicillin-binding protein 4* and an apparent amino acid racemase. J Bacteriol 175 : 2917 2925.
Popham DL, Illades-Aguiar B Setlow P (1995) The Bacillus subtilis dacB gene, encoding penicillin-binding protein 5*, is part of a three-gene operon required for proper spore cortex synthesis and spore core dehydration. J Bacteriol 177 : 4721 4729.
Popham DL, Gilmore ME Setlow P (1999) Roles of low-molecular-weight penicillin-binding proteins in Bacillus subtilis spore peptidoglycan synthesis and spore properties. J Bacteriol 181 : 126 132.
Priyadarshini R, Popham DL Young KD (2006) Daughter cell separation by penicillin-binding proteins and peptidoglycan amidases in Escherichia coli. J Bacteriol 188 : 5345 5355.
Reynolds PE, Ambur OH, Casadewall B Courvalin P (2001) The VanY(D) dd-carboxypeptidase of Enterococcus faecium BM4339 is a penicillin-binding protein. Microbiology 147 : 2571 2578.
Romeis T Holtje JV (1994a) Penicillin-binding protein 7/8 of Escherichia coli is a dd-endopeptidase. Eur J Biochem 224 : 597 604.
Romeis T Holtje JV (1994b) Specific interaction of penicillin-binding proteins 3 and 7/8 with soluble lytic transglycosylase in Escherichia coli. J Biol Chem 269 : 21603 21607.
Ropp PA, Hu M, Olesky M Nicholas RA (2002) Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 46 : 769 777.
Santos JM, Lobo M, Matos AP, De Pedro MA Arraiano CM (2002) The gene bolA regulates dacA (PBP5), dacC (PBP6) and ampC (AmpC), promoting normal morphology in Escherichia coli. Mol Microbiol 45 : 1729 1740.
Sauvage E, Kerff F, Fonzé E et al 2002) The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin. Cell Mol Life Sci 59 : 1223 1232.
Sauvage E, Herman R, Petrella S, Duez C, Bouillenne F, Frère JM Charlier P (2005) Crystal structure of the Actinomadura R39 dd-peptidase reveals new domains in penicillin-binding proteins. J Biol Chem 280 : 31249 31256.
Sauvage E, Duez C, Herman R et al 2007) Crystal structure of the Bacillus subtilis penicillin-binding protein 4a, and its complex with a peptidoglycan mimetic peptide. J Mol Biol 371 : 528 539.
Scheffers DJ (2005) Dynamic localization of penicillin-binding proteins during spore development in Bacillus subtilis. Microbiology 151 : 999 1012.
Scheffers DJ Errington J (2004) PBP1 is a component of the Bacillus subtilis cell division machinery. J Bacteriol 186 : 5153 5156.
Scheffers DJ, Jones LJ Errington J (2004) Several distinct localization patterns for penicillin-binding proteins in Bacillus subtilis. Mol Microbiol 51 : 749 764.
Schiffer G Holtje JV (1999) Cloning and characterization of PBP 1C, a third member of the multimodular class A penicillin-binding proteins of Escherichia coli. J Biol Chem 274 : 32031 32039.
Schleifer KH Kandler O (1972) Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol Rev 36 : 407 477.
Schouten JA, Bagga S, Lloyd AJ, de Pascale G, Dowson CG, Roper DI Bugg TD (2006) Fluorescent reagents for in vitro studies of lipid-linked steps of bacterial peptidoglycan biosynthesis: derivatives of UDPMurNAc-pentapeptide containing d-cysteine at position 4 or 5. Mol Biosyst 2 : 484 491.
Schwartz B, Markwalder JA Wang Y (2001) Lipid II: total synthesis of the bacterial cell wall precursor and utilization as a substrate for glycosyltransfer and transpeptidation by penicillin binding protein (PBP) 1b of Escherichia coli. J Am Chem Soc 123 : 11638 11643.
Schwartz B, Markwalder JA, Seitz SP, Wang Y Stein RL (2002) A kinetic characterization of the glycosyltransferase activity of Eschericia coli PBP1b and development of a continuous fluorescence assay. Biochemistry 41 : 12552 12561.
Shafer WM Judd RC (1991) Gonococcal penicillin-binding protein 3 and the surface-exposed 44kDa peptidoglycan-binding protein appear to be the same molecule. Mol Microbiol 5 : 1097 1103.
Silvaggi NR, Anderson JW, Brinsmade SR, Pratt RF Kelly JA (2003) The crystal structure of phosphonate-inhibited d-Ala-d-Ala peptidase reveals an analogue of a tetrahedral transition state. Biochemistry 42 : 1199 1208.
Silvaggi NR, Josephine HR, Kuzin AP, Nagarajan R, Pratt RF Kelly JA (2005) Crystal structures of complexes between the R61 dd-peptidase and peptidoglycan-mimetic beta-lactams: a non-covalent complex with a "perfect penicillin". J Mol Biol 345 : 521 533.
Spratt BG (1977) Temperature-sensitive cell division mutants of Escherichia coli with thermolabile penicillin-binding proteins. J Bacteriol 131 : 293 305.
Spratt BG (1988) Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature 332 : 173 176.
Spratt BG Cromie KD (1988) Penicillin-binding proteins of gram-negative bacteria. Rev Infect Dis 10 : 699 711.
Spratt BG Pardee AB (1975) Penicillin-binding proteins and cell shape in E. coli. Nature 254 : 516 517.
Spratt BG Strominger JL (1976) Identification of the major penicillin-binding proteins of Escherichia coli as d-alanine carboxypeptidase IA. J Bacteriol 127 : 660 663.
Spratt BG, Zhou J, Taylor M Merrick MJ (1996) Monofunctional biosynthetic peptidoglycan transglycosylases. Mol Microbiol 19 : 639 640.
Stefanova ME, Tomberg J, Olesky M, Holtje JV, Gutheil WG Nicholas RA (2003) Neisseria gonorrhoeae penicillin-binding protein 3 exhibits exceptionally high carboxypeptidase and beta-lactam binding activities. Biochemistry 42 : 14614 14625.
Stefanova ME, Tomberg J, Davies C, Nicholas RA Gutheil WG (2004) Overexpression and enzymatic characterization of Neisseria gonorrhoeae penicillin-binding protein 4. Eur J Biochem 271 : 23 32.
Suzuki H, Nishimura Y Hirota Y (1978) On the process of cellular division in Escherichia coli: a series of mutants of E. coli altered in the penicillin-binding proteins. Proc Natl Acad Sci USA 75 : 664 668.
Terrak M Nguyen-Disteche M (2006) Kinetic characterization of the monofunctional glycosyltransferase from Staphylococcus aureus. J Bacteriol 188 : 2528 2532.
Terrak M, Ghosh TK, van Heijenoort J et al 1999) The catalytic, glycosyl transferase and acyl transferase modules of the cell wall peptidoglycan- polymerizing penicillin-binding protein 1b of Escherichia coli. Mol Microbiol 34 : 350 364.
Tipper DJ Strominger JL (1965) Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-d-alanyl-d-alanine. Proc Natl Acad Sci USA 54 : 1133 1141.
van der Linden MP, de Haan L, Hoyer MA Keck W (1992) Possible role of Escherichia coli penicillin-binding protein 6 in stabilization of stationary-phase peptidoglycan. J Bacteriol 174 : 7572 7578.
van Heijenoort Y, Gomez M, Derrien M, Ayala J van Heijenoort J (1992) Membrane intermediates in the peptidoglycan metabolism of Escherichia coli: possible roles of PBP 1b and PBP 3. J Bacteriol 174 : 3549 3557.
VanNieuwenhze MS, Mauldin SC, Zia-Ebrahimi M et al 2002) The first total synthesis of lipid II: the final monomeric intermediate in bacterial cell wall biosynthesis. J Am Chem Soc 124 : 3656 3660.
Vega D Ayala JA (2006) The dd-carboxypeptidase activity encoded by pbp4B is not essential for the cell growth of Escherichia coli. Arch Microbiol 185 : 23 27.
Vicente MF, Berenguer J, de Pedro MA, Perez-Diaz JC Baquero F (1990) Penicillin binding proteins in Listeria monocytogenes. Acta Microbiol Hung 37 : 227 231.
Vollmer W Holtje JV (2004) The architecture of the murein (peptidoglycan) in gram-negative bacteria: vertical scaffold or horizontal layer(s)? J Bacteriol 186 : 5978 5987.
Vollmer W, Blanot D de Pedro M (2008a) Peptidoglycan structure and architecture. FEMS Microbiol Rev 32 : 149 167.
Vollmer W, Joris B, Charlier P Foster S (2008b) Bacteria peptidoglycan (murein) hydrolases. FEMS Microbiol Rev 32 : 259 286.
Wang QM, Peery RB, Johnson RB, Alborn WE, Yeh WK Skatrud PL (2001) Identification and characterization of a monofunctional glycosyltransferase from Staphylococcus aureus. J Bacteriol 183 : 4779 4785.
Ward JM Hodgson JE (1993) The biosynthetic genes for clavulanic acid and cephamycin production occur as a 'super-cluster' in three Streptomyces. FEMS Microbiol Lett 110 : 239 242.
Wei Y, Havasy T, McPherson DC Popham DL (2003) Rod shape determination by the Bacillus subtilis class B penicillin-binding proteins encoded by pbpA and pbpH. J Bacteriol 185 : 4717 4726.
Weiss DS, Chen JC, Ghigo JM, Boyd D Beckwith J (1999) Localization of FtsI (PBP3) to the septal ring requires its membrane anchor, the Z ring, FtsA, FtsQ, and FtsL. J Bacteriol 181 : 508 520.
Welzel P (2005) Syntheses around the transglycosylation step in peptidoglycan biosynthesis. Chem Rev 105 : 4610 4660.
Wyke AW, Ward JB, Hayes MV Curtis NA (1981) A role in vivo for penicillin-binding protein-4 of Staphylococcus aureus. Eur J Biochem 119 : 389 393.
Ye XY, Lo MC, Brunner L, Walker D, Kahne D Walker S (2001) Better substrates for bacterial transglycosylases. J Am Chem Soc 123 : 3155 3156.
Yeats C, Finn RD Bateman A (2002) The PASTA domain: a beta-lactam-binding domain. Trends Biochem Sci 27 : 438.
Young TA, Delagoutte B, Endrizzi JA, Falick AM Alber T (2003) Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nat Struct Biol 10 : 168 174.
Yuan Y, Barrett D, Zhang Y, Kahne D, Sliz P Walker S (2007) Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis. Proc Natl Acad Sci USA 104 : 5348 5353.
Zapun A, Vernet T Pinho M (2008a) The different shapes of cocci. FEMS Microbiol Rev 32 : 345 360.
Zapun A, Contreras-Martel C Vernet T (2008b) Penicillin-binding proteins and β-lactam resistance. FEMS Microbiol Rev 32 : 361 385.
Zawadzka-Skomial J, Markiewicz Z, Nguyen-Disteche M, Devreese B, Frere JM Terrak M (2006) Characterization of the bifunctional glycosyltransferase/ acyltransferase penicillin-binding protein 4 of Listeria monocytogenes. J Bacteriol 188 : 1875 1881.
Zhang QY Spratt BG (1989) Nucleotide sequence of the penicillin-binding protein 2 gene of Neisseria meningitidis. Nucleic Acids Res 17 : 5383.
Zorzi W, Zhou XY, Dardenne O et al 1996) Structure of the low-affinity penicillin-binding protein 5 PBP5fm in wild-type and highly penicillin-resistant strains of Enterococcus faecium. J Bacteriol 178 : 4948 4957.