Genomes and Genes
Summary: A hexosyltransferase involved in the transfer of disaccharide molecules to the peptidoglycan structure of the CELL WALL SKELETON. It plays an important role in the genesis of the bacterial CELL WALL.
- Yuan Y, Barrett D, Zhang Y, Kahne D, Sliz P, Walker S. Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis. Proc Natl Acad Sci U S A. 2007;104:5348-53 pubmed publisher..We report here the 2.1-A crystal structure of the peptidoglycan glycosyltransferase (PGT) domain of Aquifex aeolicus PBP1A...
- Schiffer G, Holtje J. Cloning and characterization of PBP 1C, a third member of the multimodular class A penicillin-binding proteins of Escherichia coli. J Biol Chem. 1999;274:32031-9 pubmed..Deletion of PBP1C resulted in an altered mode of murein synthesis. It is suggested that PBP1C functions in vivo as a transglycosylase only. ..
- Weiss D, Chen J, Ghigo J, Boyd D, Beckwith J. Localization of FtsI (PBP3) to the septal ring requires its membrane anchor, the Z ring, FtsA, FtsQ, and FtsL. J Bacteriol. 1999;181:508-20 pubmed..Septal localization depended upon every other division protein tested (FtsZ, FtsA, FtsQ, and FtsL). We conclude that FtsI is a late recruit to the division site, and that its localization depends on an intact membrane anchor. ..
- Ramachandran V, Chandrakala B, Kumar V, Usha V, Solapure S, de Sousa S. Screen for inhibitors of the coupled transglycosylase-transpeptidase of peptidoglycan biosynthesis in Escherichia coli. Antimicrob Agents Chemother. 2006;50:1425-32 pubmed..Surprisingly, tunicamycin and nisin also inhibited the assay, and paper chromatography analysis revealed that both inhibited the transglycosylase. The assay can be used to screen for novel antibacterial agents. ..
- Pepper E, Farrell M, Finkel S. Role of penicillin-binding protein 1b in competitive stationary-phase survival of Escherichia coli. FEMS Microbiol Lett. 2006;263:61-7 pubmed..Additionally, we present evidence that this protein, as well as AmpC, may assist in cellular resistance to beta-lactam antibiotics. ..
- Mohammadi T, Karczmarek A, Crouvoisier M, Bouhss A, Mengin Lecreulx D, Den Blaauwen T. 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. 2007;65:1106-21 pubmed..It is postulated that the involvement of MurG in the peptidoglycan synthesis concurs with two complexes, one implicated in cell elongation and the other in division. A model representing the first complex is proposed. ..
- Muller P, Ewers C, Bertsche U, Anstett M, Kallis T, Breukink E, et al. The essential cell division protein FtsN interacts with the murein (peptidoglycan) synthase PBP1B in Escherichia coli. J Biol Chem. 2007;282:36394-402 pubmed..FtsN stimulated the in vitro murein synthesis activities of PBP1B. Thus, FtsN could have a role in controlling or modulating the activity of PBP1B during cell division in Escherichia coli. ..
- Taschner P, Huls P, Pas E, Woldringh C. Division behavior and shape changes in isogenic ftsZ, ftsQ, ftsA, pbpB, and ftsE cell division mutants of Escherichia coli during temperature shift experiments. J Bacteriol. 1988;170:1533-40 pubmed..Although the ftsE mutant produced filaments in broth medium at the restrictive temperature, it cannot be considered a cell division mutant under the presently applied conditions. ..
- Vollmer W, von Rechenberg M, Holtje J. Demonstration of molecular interactions between the murein polymerase PBP1B, the lytic transglycosylase MltA, and the scaffolding protein MipA of Escherichia coli. J Biol Chem. 1999;274:6726-34 pubmed..coli. ..
- Iwai N, Nagai K, Wachi M. Novel S-benzylisothiourea compound that induces spherical cells in Escherichia coli probably by acting on a rod-shape-determining protein(s) other than penicillin-binding protein 2. Biosci Biotechnol Biochem. 2002;66:2658-62 pubmed..These results suggest that the target molecule(s) of A22 was not penicillin-binding protein 2. A22 may act on a rod-shape-determining protein(s) other than penicillin-binding protein 2, such as RodA or MreB. ..
- Ostash B, Doud E, Lin C, Ostash I, Perlstein D, Fuse S, et al. Complete characterization of the seventeen step moenomycin biosynthetic pathway. Biochemistry. 2009;48:8830-41 pubmed publisher..This work will enable both in vitro and fermentation-based reconstitution of phosphoglycolipid scaffolds so that chemoenzymatic approaches to novel analogues can be explored. ..
- Meisel U, Höltje J, Vollmer W. Overproduction of inactive variants of the murein synthase PBP1B causes lysis in Escherichia coli. J Bacteriol. 2003;185:5342-8 pubmed..A possible structural interaction between PBP1B and murein hydrolases in vivo by the formation of a multienzyme complex is discussed. ..
- Mesleh M, Rajaratnam P, Conrad M, Chandrasekaran V, Liu C, Pandya B, et al. Targeting Bacterial Cell Wall Peptidoglycan Synthesis by Inhibition of Glycosyltransferase Activity. Chem Biol Drug Des. 2016;87:190-9 pubmed publisher..we designed a library of disaccharide compounds based on the minimum moenomycin fragment with peptidoglycan glycosyltransferase inhibitory activity and based on a more drug-like and synthetically versatile disaccharide building ..
- Yunck R, Cho H, Bernhardt T. Identification of MltG as a potential terminase for peptidoglycan polymerization in bacteria. Mol Microbiol. 2016;99:700-18 pubmed publisher..Our combined results are thus consistent with a model in which MltG associates with PG synthetic complexes to cleave nascent polymers and terminate their elongation. ..
- Li S, Mo C, Peng Q, Kang X, Sun C, Jiang K, et al. Cell surface glycan alterations in epithelial mesenchymal transition process of Huh7 hepatocellular carcinoma cell. PLoS ONE. 2013;8:e71273 pubmed publisher..The findings of this study systematically clarify the alterations of cell surface glycan in cancer EMT, and may provide novel insight for HCC metastasis. ..
- Ostash B, Walker S. Bacterial transglycosylase inhibitors. Curr Opin Chem Biol. 2005;9:459-66 pubmed
- Piette A, Fraipont C, Den Blaauwen T, Aarsman M, Pastoret S, Nguyen Distèche M. Structural determinants required to target penicillin-binding protein 3 to the septum of Escherichia coli. J Bacteriol. 2004;186:6110-7 pubmed..We postulate that FtsQ could play a role in regulating the assembly of these division proteins at the division site and the activity of the peptidoglycan assembly machineries within the divisome. ..
- Ishino F, Mitsui K, Tamaki S, Matsuhashi M. Dual enzyme activities of cell wall peptidoglycan synthesis, peptidoglycan transglycosylase and penicillin-sensitive transpeptidase, in purified preparations of Escherichia coli penicillin-binding protein 1A. Biochem Biophys Res Commun. 1980;97:287-93 pubmed
- Basu J, Mahapatra S, Kundu M, Mukhopadhyay S, Nguyen Distèche M, DuBois P, et al. Identification and overexpression in Escherichia coli of a Mycobacterium leprae gene, pon1, encoding a high-molecular-mass class A penicillin-binding protein, PBP1. J Bacteriol. 1996;178:1707-11 pubmed..The solubilized PBP1 derivatives can be purified by affinity chromatography on Ni2+-nitrilotriacetic acid agarose. They have low affinities for the usual penicillins and cephalosporins. ..
- Ogura T, Tomoyasu T, Yuki T, Morimura S, Begg K, Donachie W, et al. Structure and function of the ftsH gene in Escherichia coli. Res Microbiol. 1991;142:279-82 pubmed..A wild type chromosomal fragment able to complement the sfh mutations was cloned. We also identified another gene (ftsJ) affecting cell division in the region upstream of the ftsH gene. ..
- Dalhoff A, Nasu T, Okamoto K. Target affinities of faropenem to and its impact on the morphology of gram-positive and gram-negative bacteria. Chemotherapy. 2003;49:172-83 pubmed..Thus, the high binding affinities of faropenem to PBPs from gram-negative and gram-positive bacteria are mirrored by its pronounced and concentration-dependent bactericidal effect. ..
- Leganés F, Blanco Rivero A, Fernández Piñas F, Redondo M, Fernández Valiente E, Fan Q, et al. Wide variation in the cyanobacterial complement of presumptive penicillin-binding proteins. Arch Microbiol. 2005;184:234-48 pubmed
- Hara H, Narita S, Karibian D, Park J, Yamamoto Y, Nishimura Y. Identification and characterization of the Escherichia coli envC gene encoding a periplasmic coiled-coil protein with putative peptidase activity. FEMS Microbiol Lett. 2002;212:229-36 pubmed..Disruption of the chromosomal envC caused the same defects as the envC point mutation, indicating the gene is dispensable for growth but important for normal septation/separation and cell envelope integrity...
- Hara H, Nishimura Y, Kato J, Suzuki H, Nagasawa H, Suzuki A, et al. Genetic analyses of processing involving C-terminal cleavage in penicillin-binding protein 3 of Escherichia coli. J Bacteriol. 1989;171:5882-9 pubmed..This suggests the importance of C-terminal hydrophobic regions that terminate at Leu-558 to PBP 3 functioning and the requirement of further-distal peptides for the stability of PBP 3. ..
- Wijayarathna C, Wachi M, Nagai K. Isolation of ftsI and murE genes involved in peptidoglycan synthesis from Corynebacterium glutamicum. Appl Microbiol Biotechnol. 2001;55:466-70 pubmed..Both ORFs were involved in peptidoglycan synthesis. Proteins were synthesized from the C. glutamicum murE and ftsI genes, 55 kDa and 73 kDa respectively, in an in vitro protein synthesis system, using E. coli S30 extracts. ..
- Goffin C, Fraipont C, Ayala J, Terrak M, Nguyen Distèche M, Ghuysen J. The non-penicillin-binding module of the tripartite penicillin-binding protein 3 of Escherichia coli is required for folding and/or stability of the penicillin-binding module and the membrane-anchoring module confers cell septation activity on the fo. J Bacteriol. 1996;178:5402-9 pubmed..The in vivo activity of PBP3 also depends on the M-1-to-E-56 amino-terminal module which encompasses the cytosol, the membrane, and the periplasm and which functions as a noncleaved pseudo-signal peptide. ..
- Typas A, Banzhaf M, van den Berg van Saparoea B, Verheul J, Biboy J, Nichols R, et al. Regulation of peptidoglycan synthesis by outer-membrane proteins. Cell. 2010;143:1097-109 pubmed publisher..LpoA/LpoB and their PBP-docking regions are restricted to ?-proteobacteria, providing models for niche-specific regulation of sacculus growth. ..
- Ostash B, Doud E, Fedorenko V. The molecular biology of moenomycins: towards novel antibiotics based on inhibition of bacterial peptidoglycan glycosyltransferases. Biol Chem. 2010;391:499-504 pubmed publisher..Here, we highlight the importance of research on the genetic mechanisms that regulate moenomycin biosynthesis and that confer moenomycin resistance to bacteria in the development of novel anti-infectives based on PGT inhibition. ..
- Makitrynskyy R, Ostash B, Tsypik O, Rebets Y, Doud E, MEREDITH T, et al. Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin. Open Biol. 2013;3:130121 pubmed publisherUnlike the majority of actinomycete secondary metabolic pathways, the biosynthesis of peptidoglycan glycosyltransferase inhibitor moenomycin in Streptomyces ghanaensis does not involve any cluster-situated regulators (CSRs)...
- Egan A, Biboy J, van t Veer I, Breukink E, Vollmer W. Activities and regulation of peptidoglycan synthases. Philos Trans R Soc Lond B Biol Sci. 2015;370: pubmed publisher..As an example, we demonstrate a synergistic effect of multiple protein-protein interactions on the glycosyltransferase activity of PBP1B, by its cognate lipoprotein activator LpoB and the essential cell division protein FtsN. ..
- Alexeeva S, Gadella T, Verheul J, Verhoeven G, Den Blaauwen T. Direct interactions of early and late assembling division proteins in Escherichia coli cells resolved by FRET. Mol Microbiol. 2010;77:384-98 pubmed publisher..This is in line with the recently described role of FtsN in divisome stabilization including the proto-ring elements. ..
- Hayashi S, Hara H, Suzuki H, Hirota Y. Lipid modification of Escherichia coli penicillin-binding protein 3. J Bacteriol. 1988;170:5392-5 pubmed..As expected from this finding, PBP 3 was found to be modified with glycerol and fatty acids, although the lipid modification occurred only in a small fraction, accounting for less than 15% of the total PBP 3 molecules. ..
- Karimova G, Dautin N, Ladant D. Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis. J Bacteriol. 2005;187:2233-43 pubmed..In addition, our study shows that the cAMP-based two-hybrid system is particularly appropriate for analyzing molecular interactions between membrane proteins. ..
- Ebersbach G, Galli E, Møller Jensen J, Lowe J, Gerdes K. Novel coiled-coil cell division factor ZapB stimulates Z ring assembly and cell division. Mol Microbiol. 2008;68:720-35 pubmed publisher..In vitro, ZapB self-assembled into long filaments and bundles. These results raise the possibility that ZapB stimulates Z ring formation directly via its capacity to self-assemble into larger structures. ..
- Shiomi D, Margolin W. Compensation for the loss of the conserved membrane targeting sequence of FtsA provides new insights into its function. Mol Microbiol. 2008;67:558-69 pubmed publisher..We propose that FtsA function in cell division depends on additive effects of membrane binding and self-interaction, and that the specific requirement of an amphipathic helix for tethering FtsA to the membrane can be bypassed...
- Derouaux A, Wolf B, Fraipont C, Breukink E, Nguyen Distèche M, Terrak M. The monofunctional glycosyltransferase of Escherichia coli localizes to the cell division site and interacts with penicillin-binding protein 3, FtsW, and FtsN. J Bacteriol. 2008;190:1831-4 pubmed publisherThe monofunctional peptidoglycan glycosyltransferase (MtgA) catalyzes glycan chain elongation of the bacterial cell wall...
- Bertsche U, Breukink E, Kast T, Vollmer W. In vitro murein peptidoglycan synthesis by dimers of the bifunctional transglycosylase-transpeptidase PBP1B from Escherichia coli. J Biol Chem. 2005;280:38096-101 pubmed..PBP1B was also capable of synthesizing trimeric muropeptide structures. Tri-, tetra-, and pentapeptide compounds could serve as acceptors in the PBP1B-catalyzed transpeptidation reaction. ..
- Wright G. Biochemistry. A new target for antibiotic development. Science. 2007;315:1373-4 pubmed
- Hara H, Yamamoto Y, Higashitani A, Suzuki H, Nishimura Y. Cloning, mapping, and characterization of the Escherichia coli prc gene, which is involved in C-terminal processing of penicillin-binding protein 3. J Bacteriol. 1991;173:4799-813 pubmed..The mutation resulted in greatly reduced heat shock response at low osmolarity and in leakage of periplasmic proteins. ..
- Stefanova M, Tomberg J, Olesky M, Höltje J, Gutheil W, Nicholas R. Neisseria gonorrhoeae penicillin-binding protein 3 exhibits exceptionally high carboxypeptidase and beta-lactam binding activities. Biochemistry. 2003;42:14614-25 pubmed..gonorrhoeae, although deletion of both PBP 3 and PBP 4, the other low-molecular-mass PBP in N. gonorrhoeae, resulted in a decreased growth rate and marked morphological abnormalities. ..
- Paradis Bleau C, Markovski M, Uehara T, Lupoli T, Walker S, KAHNE D, et al. Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases. Cell. 2010;143:1110-20 pubmed publisher..Overall, our results indicate that PBP accessory proteins play a central role in PG biogenesis, and like the PBPs they work with, these factors are attractive targets for antibiotic development. ..
- Derouaux A, Turk S, Olrichs N, Gobec S, Breukink E, Amoroso A, et al. Small molecule inhibitors of peptidoglycan synthesis targeting the lipid II precursor. Biochem Pharmacol. 2011;81:1098-105 pubmed publisher..These small molecules are promising leads for the development of more active and specific compounds to target the essential GT step in cell wall synthesis. ..
- Wang T, Lupoli T, Sumida Y, Tsukamoto H, Wu Y, Rebets Y, et al. Primer preactivation of peptidoglycan polymerases. J Am Chem Soc. 2011;133:8528-30 pubmed publisher..Here we show that a synthetic peptidoglycan fragment that mimics the elongating polymer chain activates peptidoglycan glycosyltransferases by bypassing the rate-limiting initiation step. ..
- Dumbre S, Derouaux A, Lescrinier E, Piette A, Joris B, Terrak M, et al. Synthesis of modified peptidoglycan precursor analogues for the inhibition of glycosyltransferase. J Am Chem Soc. 2012;134:9343-51 pubmed publisher..The more active was C16-phosphoglycerate-MurNAc-(L-Ala-D-Glu)-GlcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors. ..
- Laubacher M, Melquist A, Chandramohan L, Young K. Cell sorting enriches Escherichia coli mutants that rely on peptidoglycan endopeptidases to suppress highly aberrant morphologies. J Bacteriol. 2013;195:855-66 pubmed publisher..The results validate the use of cell sorting as a means for studying bacterial morphology and identify at least one new class of enzymes required for the suppression of cell shape defects. ..
- Lebar M, Lupoli T, Tsukamoto H, May J, Walker S, Kahne D. Forming cross-linked peptidoglycan from synthetic gram-negative Lipid II. J Am Chem Soc. 2013;135:4632-5 pubmed publisher..This work provides the tools necessary for reconstituting cell wall synthesis, an essential cellular process and major antibiotic target, in a purified system. ..
- Gray A, Egan A, Van t Veer I, Verheul J, Colavin A, Koumoutsi A, et al. Coordination of peptidoglycan synthesis and outer membrane constriction during Escherichia coli cell division. elife. 2015;4: pubmed publisher..Coordination of the PBP1B and Tol machines by CpoB contributes to effective PBP1B function in vivo and maintenance of cell envelope integrity during division. ..
- Buddelmeijer N, Judson N, Boyd D, Mekalanos J, Beckwith J. YgbQ, a cell division protein in Escherichia coli and Vibrio cholerae, localizes in codependent fashion with FtsL to the division site. Proc Natl Acad Sci U S A. 2002;99:6316-21 pubmed publisher..coli. Our results show colocalization of proteins to the bacterial midcell in E. coli and raise the possibility that these proteins interact in a coiled-coil structure...
- Knerr P, Oman T, Garcia De Gonzalo C, Lupoli T, Walker S, van der Donk W. Non-proteinogenic amino acids in lacticin 481 analogues result in more potent inhibition of peptidoglycan transglycosylation. ACS Chem Biol. 2012;7:1791-5 pubmed publisher..Additionally, we demonstrate that lacticin 481 does not form pores in the membranes of susceptible bacteria, a common mode-of-action of other lantibiotics. ..
- Huang S, Wu W, Huang L, Huang W, Fu W, Chen P, et al. New continuous fluorometric assay for bacterial transglycosylase using Förster resonance energy transfer. J Am Chem Soc. 2013;135:17078-89 pubmed publisher..This new continuous fluorescent assay not only provides an efficient and convenient way to study TGase activities, but also enables the high-throughput screening of potential TGase inhibitors for antibiotic discovery. ..
- Zijderveld C, Aarsman M, Nanninga N. Differences between inner membrane and peptidoglycan-associated PBP1B dimers of Escherichia coli. J Bacteriol. 1995;177:1860-3 pubmed..The second class, like the monomeric form of PBP1B, could be isolated with the inner membrane fraction. This dimeric form dissociated in the presence of zinc in combination with beta-mercaptoethanol. ..
- Barrett D, Wang T, Yuan Y, Zhang Y, Kahne D, Walker S. Analysis of glycan polymers produced by peptidoglycan glycosyltransferases. J Biol Chem. 2007;282:31964-71 pubmed..The assay and results described provide new information about the process by which PGTs assemble bacterial cell walls. ..
- Yuan Y, Fuse S, Ostash B, Sliz P, Kahne D, Walker S. Structural analysis of the contacts anchoring moenomycin to peptidoglycan glycosyltransferases and implications for antibiotic design. ACS Chem Biol. 2008;3:429-36 pubmed publisher..This compound has comparable biological activity to the previously proposed minimal pharmacophore. The results reported here may facilitate the design of antibiotics targeted against peptidoglycan glycosyltransferases. ..