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Penicillin-Binding Proteins (PBPs) and Bacterial Cell Wall Elongation Complexes

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Macromolecular Protein Complexes II: Structure and Function

Part of the book series: Subcellular Biochemistry ((SCBI,volume 93))

Abstract

The bacterial cell wall is the validated target of mainstream antimicrobials such as penicillin and vancomycin. Penicillin and other β-lactams act by targeting Penicillin-Binding Proteins (PBPs), enzymes that play key roles in the biosynthesis of the main component of the cell wall, the peptidoglycan. Despite the spread of resistance towards these drugs, the bacterial cell wall continues to be a major Achilles’ heel for microbial survival, and the exploration of the cell wall formation machinery is a vast field of work that can lead to the development of novel exciting therapies. The sheer complexity of the cell wall formation process, however, has created a significant challenge for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. New developments in genetic and biochemical screens, as well as different aspects of structural biology, have shed new light on the importance of complexes formed by PBPs, notably within the cell wall elongation machinery. This chapter summarizes structural and functional details of PBP complexes involved in the periplasmic and membrane steps of peptidoglycan biosynthesis with a focus on cell wall elongation. These assemblies could represent interesting new targets for the eventual development of original antibacterials.

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References

  • Alexander JAN, Chatterjee SS, Hamilton SM, Eltis LD, Chambers HF, Strynadka NC (2018) Structural and kinetic analyses of penicillin-binding protein 4 (PBP4)-mediated antibiotic resistance in Staphylococcus aureus. J Biol Chem 293:19854–19865

    Article  PubMed  PubMed Central  Google Scholar 

  • Barreteau H, Kovac A, Boniface A, Sova M, Gobec S, Blanot D (2008) Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiol Rev 32:168–207

    Article  CAS  PubMed  Google Scholar 

  • Bernardo-García N, Mahasenan KV, Batuecas MT, Lee M, Hesek D, Petráčková D, Doubravová L, Branny P, Mobashery S, Hermoso JA (2018) Allostery, recognition of nascent peptidoglycan, and cross-linking of the cell Wall by the essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae. ACS Chem Biol 13:694–702

    Article  CAS  PubMed  Google Scholar 

  • Bouhss A, Crouvoisier M, Blanot D, Mengin-Lecreulx D (2004) Purification and characterization of the bacterial MraY translocase catalyzing the first membrane step of peptidoglycan biosynthesis. J Biol Chem 279:29974–29980

    Article  CAS  PubMed  Google Scholar 

  • Cho H, Wivagg CN, Kapoor M, Barry Z, Rohs PD, Suh H, Marto JA, Garner EC, Bernhardt TG (2016) Bacterial cell wall biogenesis is mediated by SEDS and PBP polymerase families functioning semi-autonomously. Nat Microbiol 19:16172

    Article  CAS  Google Scholar 

  • Chung BC, Mashalidis EH, Tanino T, Kim M, Matsuda A, Hong J, Ichikawa S, Lee SY (2016) Structural insights into inhibition of Lipid I production in bacterial cell wall synthesis. Nature 533:557–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung BC, Zhao J, Gillespie RA, Kwon D-Y, Guan Z, Hong J, Zhou P, Lee S-Y (2013) Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. Science 341:1012–1016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Contreras-Martel C, Amoroso A, Woon ECY, Zervosen A, Inglis S, Martins A, Verlaine O, Rydzik AM, Job V, Luxen A, Joris B, Schofield CJ, Dessen A (2011) Structure-guided design of cell wall biosynthesis inhibitors that overcome β-lactam resistance in Staphylococcus aureus (MRSA). ACS Chem Biol 6:943–951

    Article  CAS  PubMed  Google Scholar 

  • Contreras-Martel C, Dahout-Gonzalez C, Dos Santos Martins A, Kotnik M, Dessen A (2009) PBP active site flexibility as the key mechanism for beta-lactam resistance in pneumococci. J Mol Biol 387:899–909

    Article  CAS  PubMed  Google Scholar 

  • 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 b-lactam resistance in Streptococcus pneumoniae. J Mol Biol 355:684–696

    Article  CAS  PubMed  Google Scholar 

  • Contreras-Martel C, Martins A, Ecobichon C, Trindade DM, Mattei PJ, Hicham S, Hardouin P, Ghachi M, Boneca IG, Dessen A (2017) Molecular architecture of the PBP2-MreC core bacterial cell wall synthesis complex. Nature Commun 8:776

    Article  CAS  Google Scholar 

  • den Blaauwen T, de Pedro MA, Nguyen-Distèche M, Ayala JA (2008) Morphogenesis of rod-shaped sacculi. FEMS Microbiol Rev 32:321–344

    Article  CAS  Google Scholar 

  • Divakaruni AV, Baida C, White CL, Gober JW (2007) The cell shape proteins MreB and MreC control cell morphogenesis by positioning cell wall synthetic complexes. Mol Microbiol 66:174–188

    Article  CAS  PubMed  Google Scholar 

  • Divakaruni AV, Ogorzalek Loo RR, Xie Y, Loo JA, Gober JW (2005) The cell-shape protein MreC interacts with extracytoplasmic proteins including cell wall assembly complexes in Caulobacter crescentus. Proc Natl Acad Sci USA 51:18602–18607

    Article  CAS  Google Scholar 

  • Dye NA, Pincus Z, Theriot JA, Shapiro L, Gitai Z (2005) Two independent spiral structures control cell shape in Caulobacter. Proc Natl Acad Sci USA 102:18608–18613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egan AJ, Cleverley RM, Peters K, Lewis RJ, Vollmer W (2017) Regulation of bacterial cell wall growth. FEBS J 284:851–867

    Article  CAS  PubMed  Google Scholar 

  • Egan AJF, Maya-Martinez R, Ayala I, Bougault CM, Banzhaf M, Breukink E, Vollmer W, Simorre JP (2018) Induced conformational changes activate the peptidoglycan synthase PBP1b. Mol Microbiol 110:335–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El Ghachi M, Matteï PJ, Ecobichon C, Martins A, Hoos S, Schmitt C, Colland F, Ebel C, Prevost MC, Gabel F, Dessen A, Boneca IG (2011) Characterization of the elongasome core PBP2: MreC complex of Helicobacter pylori. Mol Microbiol 82:68–86

    Article  CAS  PubMed  Google Scholar 

  • Elhenawy W, Davis RM, Fero J, Salama NR, Felman MF, Ruiz N (2016) The O-antigen flippase Wzk can substitute for MurJ in peptidoglycan synthesis in Helicobacter pylori and Escherichia coli. PLoS ONE 11:e0161587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ema M, Xu Y, Gehrke S, Wagner GK (2017) Identification of non-substrate-like glycosyltransferase inhibitors from library screening: Pitfalls & hits. Med Chem Comm 9:131–137

    Article  Google Scholar 

  • Fay A, Meyer P, Dworkin J (2010) Interactions between late-acting proteins required for peptidoglycan synthesis during sporulation. J Mol Biol 399:547–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fedarovich A, Djordjevic KA, Swanson SM, Peterson YK, Nicholas RA, Davies C (2012) High-throughput screening for novel inhibitors of Neisseria gonorrhoeae penicillin-binding protein 2. PLoS ONE 7:e44918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fenton AK, El Mortaji L, Lau DTC, Rudner DZ, Bernhardt TG (2016) CozE is a member of the MreCD complex that directs cell elongation in Streptococcus pneumoniae. Nat Microbiol 2:16237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Figge RM, Divakaruni AV, Gober JW (2004) MreB, the cell shape-determining bacterial actin homologue, coordinates cell wall morphogenesis in Caulobacter crescentus. Mol Microbiol 51:1321–1332

    Article  CAS  PubMed  Google Scholar 

  • Fraipont C, Alexeeva S, Wolf B, van der Ploeg R, Schloesser M, den Blaauwen T, Nguyen-Distèche M (2011) The integral membrane FtsW protein and peptidoglycan synthase PBP3 form a subcomplex in Escherichia coli. Microbiology 157:251–259

    Article  CAS  PubMed  Google Scholar 

  • Goffin C, Ghuysen JM (2002) Biochemistry and comparative genomics of SXXK superfamily acyltransferases offer a clue to the mycobacterial paradox. Microb Mol Biol Rev 66:702–738

    Article  CAS  Google Scholar 

  • Goldman RC, Gange D (2000) Inhibition of transglycosylation involved in bacterial peptidoglycan synthesis. Curr Med Chem 7:801–820

    Google Scholar 

  • Hakulinen JK, Hering J, Brändén G, Chen H, Snijder A, Ek M, Johansson P (2017) MraY-antibiotic complex reveals details of tunicamycin mode of action. Nat Chem Biol 13:265–267

    Article  CAS  PubMed  Google Scholar 

  • Höltje JV (1998) Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli. Microbiol Mol Biol Rev 62:181–203

    Article  PubMed  PubMed Central  Google Scholar 

  • Hugonnet JE, Mengin-Lecreulx D, Monton A, den Blaauwen T, Carbonnelle E, Veckerlé C, Brun YV, van Niewenhze M, Bouchier C, Tu K, Rice LB, Arthur M (2016) Factors essential for L, D-transpeptidase-mediated peptidoglycan cross-linking and β-lactam resistance in Escherichia coli. Elife 5:e19469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong J-H, Kim Y-S, Rojviriya C, Ha S-C, Kang BS, Kim Y-G (2013) Crystal structures of bifunctional Penicillin-Binding Protein 4 from Listeria monocytogenes. Antimicrob Agents Chemother 57:3507–3512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King DT, Wasney GA, Nosella M, Fong A, Strynadka NC (2017) Structural insights into inhibition of Escherichia coli Penicillin-Binding Protein 1b. J Biol Chem 292:979–993

    Article  CAS  PubMed  Google Scholar 

  • Kocaoglu O, Tsui HC, Winkler ME, Carlson EE (2015) Profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39. Antimicrob Agents Chemother 59:3548–3555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kruse T, Bork-Jensen J, Gerdes K (2005) The morphogenetic MreBCD proteins of Escherichia coli form an essential membrane-bound complex. Mol Microbiol 55:78–89

    Article  CAS  PubMed  Google Scholar 

  • Kuk AC, Mashalidis EH, Lee SY (2017) Crystal structure of the MOP flippase MurJ in an inward-facing conformation. Nat Struct Mol Biol 24:171–176

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Rubino FA, Mendoza AG, Ruiz N (2019) The bacterial lipid II flippase MurJ functions by an alternating-access mechanism. J Biol Chem 294:981–990

    Article  CAS  PubMed  Google Scholar 

  • Leaver M, Errington J (2005) Roles for MreC and MreD proteins in helical growth of the cylindrical cell wall in Bacillus subtilis. Mol Microbiol 57:1196–1209

    Article  CAS  PubMed  Google Scholar 

  • Leclercq S, Derouaux A, Olatunji S, Fraipont C, Egan AJ, Vollmer W, Breukink E, Terrak M (2017) Interplay between Penicillin-Binding Proteins and SEDS proteins promotes bacterial cell wall synthesis. Sci Rep 7:43306

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee TK, Tropini C, Hsin J, Desmarais SM, Ursell TS, Gong E, Gitai Z, Monds RD, Huang KC (2014) A dynamically assembled cell wall synthesis machinery buffers cell growth. Proc Natl Acad Sci USA 111:4554–4559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim D, Strynadka NC (2002) Structural basis for the beta lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat Struct Biol 9(11):870–876

    CAS  PubMed  Google Scholar 

  • Liu Y, Breukink E (2016) The membrane steps of bacterial cell wall synthesis as antibiotic targets. Antibiotics (Basel) 5:E28

    Article  CAS  Google Scholar 

  • Liu X, Meiresonne NY, Bouhss A, den Blaauwen T (2018) FtsW activity and Lipid II synthesis are required for recruitment of MurJ to midcell during cell division in Escherichia coli. Mol Microbiol 109:865–884

    Article  CAS  Google Scholar 

  • Lloyd AJ, Brandish PE, Gilbey AM, Bugg TD (2004) Phospho-N-acetyl-muramyl-pentapeptide translocase from Escherichia coli: catalytic role of conserved aspartic acid residues. J Bacteriol 186:1747–1757

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Lovering AL, Safadi SS, Strynadka NCJ (2012) Structural perspective of peptidoglycan biosynthesis and assembly. Annu Rev Biochem 81:451–478

    Article  CAS  PubMed  Google Scholar 

  • 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(5):673–691

    Article  CAS  PubMed  Google Scholar 

  • 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(3):577–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Macheboeuf P, Fischer DS, Brown T Jr, Zervosen A, Luxen A, Joris B, Dessen A, Schofield CJ (2007) Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins. Nat Chem Biol 3:565–569

    Article  CAS  PubMed  Google Scholar 

  • Matteï P-J, Neves D, Dessen A (2010) Bridging cell wall biosynthesis and bacterial morphogenesis. Curr Opin Struct Biol 20:749–766

    Article  CAS  PubMed  Google Scholar 

  • Meeske AJ, Riley EP, Robins WP, Uehara T, Mekalanos JJ, Kahne D, Walker S, Kruse AC, Bernhardt TG, Rudner DZ (2016) SEDS proteins are a widespread family of bacterial cell wall polymerases. Nature 537:634–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meeske AJ, Sham LT, Kimsey H, Koo BM, Gross CA, Bernhardt TG, Rudner DZ (2015) MurJ and a novel lipid II flippase are required for cell wall biogenesis in Bacillus subtilis. Proc Natl Acad Sci USA 112:6437–6442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohammadi T, Karczmarek A, Crouvoisier M, Bouhss A, Mengin-Lecreulx D, den Blaauwen T (2007) The essential peptidoglycan glycosyltransferase MurG forms a complex with proteins involved in lateral envelope growth as well as with proteins involved in cell division in Escherichia coli. Mol Microbiol 65:1106–1121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohammadi T, Sijbrandi R, Lutters M, Verheul J, Martin NI, den Blaauwen T, de Kruijff B, Breukink E (2014) Specificity of the transport of lipid II by FtsW in Escherichia coli. J Biol Chem 289:14707–14718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohammadi T, van Dam V, Sijbrandi R, Vernet T, Zapun A, Bouhss A, Diepeveen-de Bruin M, Nguyen-Disteche M, de Kruijff B, Breukink E (2011) Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J 30:1425–1432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moon TM, D’Andréa ED, Lee CW, Soares A, Jakoncic J, Desbonnet C, Garcia-Solache M, Rice LB, Page R, Peti W (2018) The structures of penicillin-binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into β-lactam resistance. J Biol Chem 293:18574–18584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikolaidis I, Favini-Stabile S, Dessen A (2014) Resistance to antibiotics targeted to the bacterial cell wall. Protein Sci 23:243–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikolaidis I, Izoré T, Job V, Thielens N, Breukink E, Dessen A (2012) Calcium-dependent complex formation between PBP2 and lytic transglycosylate SltB1 of Pseudomonas aeruginosa. Microb Drug Resist 18:298–305

    Article  CAS  PubMed  Google Scholar 

  • Otero LH, Rojas-Altuve A, Llarrull LI, Carrasco-López C, Kumarasiri M, Lastochkin E, Fishovitz J, Dawley M, Hesek D, Lee M, Johnson JW, Fisher JF, Chang M, Mobashery S, Hermoso JA (2013) How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function. Proc Natl Acad Sci USA 110:16808–16813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paradis-Bleau C, Markovski M, Uehara T, Lupoli TJ, Walker S, Kahne DE, Bernhardt TG (2010) Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases. Cell 143:1110–1120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pazos M, Peters K, Vollmer W (2017) Robust peptidoglycan growth by dynamic and variable multi-protein complexes. Curr Opin Microbiol 36:55–61

    Article  CAS  PubMed  Google Scholar 

  • Pernot L, Chesnel L, Le Gouellec A, Croize J, Vernet T, Dideberg O, Dessen A (2004) A PBP2x from a clinical isolate of Streptococcus pneumoniae exhibits an alternative mechanism for reduction of susceptibility to b-lactam antibiotics. J Biol Chem 279:16463–16470

    Article  CAS  PubMed  Google Scholar 

  • Rohs PDA, Buss J, Sim SI, Squyres GR, Srisuknimit V, Smith M, Cho H, Sjodt M, Kruse AC, Garner EC, Walker S, Kahne DE, Bernhardt TG (2018) A central role for PBP2 in the activation of peptidoglycan polymerization by the bacterial cell elongation machinery. PLoS Genet 14:e1007726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sham LT, Butler EK, Lebar MD, Kahne D, Bernhardt TG, Ruiz N (2014) MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis. Science 345:220–222

    Google Scholar 

  • Sjodt M, Brock K, Dobihal G, Rohs PDA, Green AG, Hopf TA, Meeske AJ, Srisuknimit V, Kahne D, Walker S, Marks DS, Bernhardt TG, Rudner DZ, Kruse AC (2018) Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis. Nature 556:118–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slovak PM, Porter SL, Armitage JP (2006) Differential localization of Mre proteins with PBP2 in Rhodobacter sphaeroides. J Bacteriol 188:1691–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung M-T, Lai Y-T, Huang C-Y, Chou L-Y, Shih H-W, Cheng W-C, Wong C-H, Ma C (2009) Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli. Proc Natl Acad Sci USA 106:8824–8829

    Article  PubMed  PubMed Central  Google Scholar 

  • Tanino T, Al-Dabbagh B, Mengin-Lecreulx D, Bouhss A, Oyama H, Ichikawa S, Matsuda A (2011) Mechanistic analysis of muraymycin analogues: a guide to the design of MraY inhibitors. J Med Chem 54:8421–8439

    Article  CAS  PubMed  Google Scholar 

  • Trip E, Scheffers D-J (2015) A 1MDa protein complex containing critical components of the Escherichia coli divisome. Sci Rep 5:18190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Typas A, Banzhaf M, Gross CA, Vollmer W (2012) From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 10:123–136

    Article  CAS  Google Scholar 

  • Typas A, Banzhaf M, van den Berg van Saparoea B, Verheul J, Bilboy J, Nichols RJ, Zietek M, Beilharz K, Kannenberg K, von Rechenberg M, Breukink E, den Blaauwen T, Gross CA, Vollmer W (2010) Regulation of peptidoglycan synthesis by outer-membrane proteins. Cell 143:1097–1109

    Google Scholar 

  • van den Ent F, Leaver M, Bendezú F, Errington J, de Boer P, Löwe J (2006) Dimeric structure of the cell shape protein MreC and its functional implications. Mol Microbiol 62:1631–1642

    Article  CAS  PubMed  Google Scholar 

  • van der Akker F, Bonomo RA (2018) Exploring additional dimensions of complexity in inhibitor design for serine β-lactamases: mechanistic and intra- and inter-molecular chemistry approaches. Front Microbiol 9:622

    Article  PubMed  PubMed Central  Google Scholar 

  • Vats P, Shigh Y-L, Rothfield L (2009) Assembly of the MreB-associated cytoskeletal ring of Escherichia coli. Mol Microbiol 72:170–182

    Article  CAS  PubMed  Google Scholar 

  • Vollmer W, Blanot D, de Pedro MA (2008) Peptidoglycan structure and architecture. FEMS Microbiol Rev 32:149–167

    Article  CAS  PubMed  Google Scholar 

  • Walsh C (2003) Where will new antibiotics come from? Nat Rev Microbiol 1:65–70

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Chan FY, Sun N, Lui HK, So PK, Yan SC, Chan KF, Chiou J, Chen S, Abagyan R, Leung YC, Wong KY (2014) Structure-based design, synthesis, and biological evaluation of isatin derivatives as potential glycosyltransferase inhibitors. Chem Biol Drug Des 84:685–696

    Article  CAS  PubMed  Google Scholar 

  • White CL, Kitich A, Gober JW (2010) Positioning cell wall synthetic complexes by the bacterial morphogenetic proteins MreB and MreD. Mol Microbiol 76:616–633

    Article  CAS  PubMed  Google Scholar 

  • Wu WS, Cheng WC, Cheng TR, Wong CH (2018) Affinity-based screen for inhibitors of bacterial transglycosylase. J Am Chem Soc 140:2752–2755

    Article  CAS  PubMed  Google Scholar 

  • Zervosen A, Herman R, Kerff f, Herman A, Bouillez a, Prati F, Pratt RF, Frère J-M, Joris B, Luxen A, Charlier P, Sauvage E (2011) Unexpected tricovalent binding mode of boronic acids within the active site of a penicillin-binding protein. J Am Chem Soc 133:10839–10848

    Google Scholar 

  • Zhang W, Ntai I, Bolla ML, Malcolmson SJ, Kahne D, Kelleher NL, Walsh CT (2011) Nine enzymes are required for assembly of the pacidamycin group of peptidyl nucleoside antibiotics. J Am Chem Soc 133:5240–5243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng S, Sham LT, Rubino FA, Brock KP, Robins WP, Mekalanos JJ, Marks DS, Bernhardt TG, Kruse AC (2018) Structure and mutagenic analysis of the lipid II flippase MurJ from Escherichia coli. Proc Natl Acad Sci USA 115:6709–6714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work in the Dessen lab on Penicillin-Binding Proteins and cell wall elongation complexes is supported by grants from the Agence Nationale de la Recherche (ANR-18-CE11-0019), FAPESP (São Paulo Research Foundation) grant 2017/12,436-9, and the Laboratoire Intenational Associé (LIA) BACWALL (CNRS). M. M. M. was supported by grant 2013/02451-0 from FAPESP.

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Miyachiro, M.M., Contreras-Martel, C., Dessen, A. (2019). Penicillin-Binding Proteins (PBPs) and Bacterial Cell Wall Elongation Complexes. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes II: Structure and Function . Subcellular Biochemistry, vol 93. Springer, Cham. https://doi.org/10.1007/978-3-030-28151-9_8

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