Table 1.
Peptidoglycan synthesis enzymes and cell morphogenesis proteins in Escherichia coli
| Function | Activity or category | Proteins* | Relevant features and remarks‡ | |
|---|---|---|---|---|
| Precursor synthesis | Transferase and dehydrogenase, respectively | MurA, MurB | • Synthesis of UDP-MurNAc from UDP-GlcNAc | |
| Amino acid ligases | MurC, MurD, MurE, MurF, Ddl | • Cytoplasmic steps leading to the UDP-MurNAc pentapeptide | ||
| Racemases | Alr, DadX, MurI | • Synthesis of D-Ala or D-Glu from L-Ala or L-Glu, respectively | ||
| GTases | MraY, MurG | • Inner membrane-localized steps of lipid II synthesis from the UDP-MurNAc pentapeptide | ||
| Peptidoglycan synthesis | GTases and DD-TPases (class A PBPs) | PBP1A | • Major peptidoglycan synthase, mainly involved in cell elongation • Anchored in the inner membrane • Interacts with LpoA |
|
| PBP1B | • Major peptidoglycan synthase, mainly involved in cell division • Anchored in the inner membrane • Dimerizes and interacts with PBP3, FtsN, MipA and LpoB • Crystal structure available |
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| PBP1C | • Cellular role unknown • Anchored in the inner membrane |
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| DD-TPases (class B PBPs) | PBP2 | • Essential for cell elongation • Dependent on MreB filament for localization • Anchored in the inner membrane |
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| PBP3 | • Essential for cell division • Part of the divisome • Anchored in the inner membrane • Interacts with PBP1B, MtgA, FtsQLB, FtsW and FtsN |
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| GTase | MtgA | • Localizes to the division site • Interacts with PBP3, FtsW and FtsN • Anchored in the inner membrane |
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| Regulation of peptidoglycan synthesis | Activators of peptidoglycan synthase | LpoA, LpoB | • Regulate PBP1A (LpoA) and PBP1B (LpoB) TPase activity • Outer-membrane lipoproteins |
|
| Formation of 3–3 crosslinks | LD-TPases | YnhG,YcbB | • Form the minor type of β-lactam-insensitive peptide crosslinks, the function of which is unknown | |
| Cell envelope stability and the creation of a firm connection between peptidoglycan and the outer membrane | Structural protein | Lpp (Braun’s lipoprotein) | • Outer-membrane lipoprotein • The bound form is covalently attached to peptidoglycan • The free form forms trimers and is embedded in the outer membrane |
|
| LD-TPases | ErfK, YbiS, YcfS | • Attachment of Lpp to peptidoglycan | ||
| Regulation of peptidoglycan structure | DD-CPases (class C PBPs) | PBP5, PBP4B, PBP6, PBP6B | • Proposed regulatory role in peptidoglycan synthesis by removal of excess pentapeptide donors in newly made peptidoglycan | |
| Peptidoglycan hydrolysis (autolysis) | DD-EPases | PBP4, PBP7 | • Septum cleavage (PBP7) • Biofilm formation (PBP7) • Also has DD-CPase activity (PBP4) |
|
| DD-and LD-EPase | MepA | • LAS family metallopeptidase | ||
| LTs | Slt70, MltA, MltB, MltC, MltD, MltE (also known as EmtA), MltF | • Major autolysins • Interact with PBP7 (Slt70) or PBP1B via MipA (MltA) • Septum cleavage (Slt70, MltA, MltB, MltC, MltD) • Outer membrane-anchored lipoproteins (Mlt proteins) |
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| Amidases | AmiA, AmiB, AmiC, AmiD | • Septum cleavage (AmiA, AmiB and AmiC) | ||
| Regulation of peptidoglycan hydrolysis | Activators of amidases | EnvC, NlpD, YgeR, YebA | • Have a LytM peptidoglycan-binding domain • Activators of AmiA and AmiB (EnvC) or AmiC (NlpD) • The roles of YgeR and YebA are unknown |
|
| Inhibitor of LTs | Ivy | • Inhibitor of MltB | ||
| Cell elongation | Cytoskeletal structure, ATPase, GTPase | MreB | • Actin structural homologue • Forms a cytoplasmic, membrane-attached helix or patches |
|
| MreB-associated proteins | MreC, MreD, RodZ, RodA, PBP2 | • MreB-associated and inner membrane-associated proteins (MreC, MreD and RodZ) • Lipid II flippase (RodA) |
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| Cell division | Cytoskeletal structure, GTPase | FtsZ | • Tubulin structural homologue • Forms a dynamic cytoplasmic ring structure at midcell |
|
| ‘Early’ association with the Z ring | FtsA, ZipA, ZapA, ZapB, ZapC, FtsE, FtsX, FtsK | • Stabilization and membrane-attachment of FtsZ polymers (FtsA, ZipA, ZapA, ZapB, ZapC) • Recruitment of proteins and DNA transport (FtsK) |
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| ‘Late’ association with the Z ring | FtsQ, FtsL, FtsB, FtsW, FtsN, PBP3, DamX, DedD, RlpA | • Interactions with peptidoglycan synthases PBP3 (FtsQLB, FtsW and FtsN) and PBP1B (PBP3 and FtsN) • Lipid II flippase (FtsW) • Peptidoglycan binding (FtsN, DamX, DedD and RlpA) |
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| Outer-membrane invagination | TolQ, TolR, TolA, TolB, Pal | • Form an envelope-spanning complex for outer-membrane invagination during septation • Peptidoglycan binding (Pal) |
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Alr, Ala racemase, biosynthetic; CPase, carboxypeptidase; DadX, Ala racemase, catabolic; Ddl, D-Ala–D-Ala ligase; EPase, endopeptidase; GlcNAc, N-acetlyglucosamine; GTase, glycosyltransferase; Ivy, inhibitor of vertebrate lysozyme; LT, lytic transglycosylase; Mlt, membrane-bound lytic murein transglycosylase; MraY, UDP-MurNAc-pentapeptide phosphotransferase; MurA, UDP-GlcNAc enolpyruvyl transferase; MurB, UDP-MurNAc dehydrogenase; MurC, UDP-MurNAc–L-Ala ligase; MurD, UDP-MurNAc-L-Ala–D-Glu ligase; MurE, UDP-MurNAc-L-Ala-D-Glu–meso-diaminopimelic acid ligase; MurF, UDP-MurNAc-tripeptide–D-alanyl-D-Ala ligase; MurG, UDP-GlcNAc-undecaprenoyl-pyrophosphoryl-MurNAc-pentapeptide transferase; MurI, Glu racemase; MurNAc, N-acetylmuramic acid; PBP, penicillin-binding protein; TPase, transpeptidase. *Proteins were assigned to one category, although many of them would fit into more than one category. The DD-TPases (class B PBPs) were added to peptidoglycan synthesis and to cell elongation (PBP2) or cell division (PBP3) to illustrate their specific functions in the cell cycle. ‡References are given in the main text.