Bulgecin C
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| Category | Others |
| Catalog number | BBF-00187 |
| CAS | 92953-56-5 |
| Molecular Weight | 444.41 |
| Molecular Formula | C14H24N2O12S |
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Description
Bulgecin C is an amino sugar produced by Pseudomonas acidophila G63O2 and P. mewacidophila SB 72310. It has Bulge-inducing activity, which can enhance the lysis of lactam antibiotics.
Specification
| Synonyms | 4-({2-Deoxy-2-[(1-hydroxyethylidene)amino]-4-O-sulfohexopyranosyl}oxy)-5-(hydroxymethyl)proline; L-Proline, 4-((2-(acetylamino)-2-deoxy-4-O-sulfo-beta-D-glucopyranosyl)oxy)-5-(hydroxymethyl)-, (2alpha,4alpha,5beta)- |
| IUPAC Name | 4-[3-acetamido-4-hydroxy-6-(hydroxymethyl)-5-sulfooxyoxan-2-yl]oxy-5-(hydroxymethyl)pyrrolidine-2-carboxylic acid |
| Canonical SMILES | CC(=O)NC1C(C(C(OC1OC2CC(NC2CO)C(=O)O)CO)OS(=O)(=O)O)O |
| InChI | InChI=1S/C14H24N2O12S/c1-5(19)15-10-11(20)12(28-29(23,24)25)9(4-18)27-14(10)26-8-2-6(13(21)22)16-7(8)3-17/h6-12,14,16-18,20H,2-4H2,1H3,(H,15,19)(H,21,22)(H,23,24,25) |
| InChI Key | FKTBPFXEHOYGEZ-UHFFFAOYSA-N |
Reference Reading
1. TraG encoded by the pIP501 type IV secretion system is a two-domain peptidoglycan-degrading enzyme essential for conjugative transfer
Karsten Arends, Ertugrul-Kaan Celik, Ines Probst, Nikolaus Goessweiner-Mohr, Christian Fercher, Lukas Grumet, Cem Soellue, Mohammad Yaser Abajy, Tuerkan Sakinc, Melanie Broszat, Katarzyna Schiwon, Guenther Koraimann, Walter Keller, Elisabeth Grohmann J Bacteriol. 2013 Oct;195(19):4436-44. doi: 10.1128/JB.02263-12. Epub 2013 Aug 2.
pIP501 is a conjugative broad-host-range plasmid frequently present in nosocomial Enterococcus faecalis and Enterococcus faecium isolates. We focus here on the functional analysis of the type IV secretion gene traG, which was found to be essential for pIP501 conjugative transfer between Gram-positive bacteria. The TraG protein, which localizes to the cell envelope of E. faecalis harboring pIP501, was expressed and purified without its N-terminal transmembrane helix (TraGΔTMH) and shown to possess peptidoglycan-degrading activity. TraGΔTMH was inhibited by specific lytic transglycosylase inhibitors hexa-N-acetylchitohexaose and bulgecin A. Analysis of the TraG sequence suggested the presence of two domains which both could contribute to the observed cell wall-degrading activity: an N-terminal soluble lytic transglycosylase domain (SLT) and a C-terminal cysteine-, histidine-dependent amidohydrolases/peptidases (CHAP) domain. The protein domains were expressed separately, and both degraded peptidoglycan. A change of the conserved glutamate residue in the putative catalytic center of the SLT domain (E87) to glycine resulted in almost complete inactivity, which is consistent with this part of TraG being a predicted lytic transglycosylase. Based on our findings, we propose that TraG locally opens the peptidoglycan to facilitate insertion of the Gram-positive bacterial type IV secretion machinery into the cell envelope.
2. Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics
Shusuke Tomoshige, David A Dik, Masaaki Akabane-Nakata, Chinedu S Madukoma, Jed F Fisher, Joshua D Shrout, Shahriar Mobashery ACS Infect Dis. 2018 Jun 8;4(6):860-867. doi: 10.1021/acsinfecdis.8b00105. Epub 2018 May 7.
The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a cobiosynthesized β-lactam antibiotic. β-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by β-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis. We describe a practical synthesis of the three naturally occurring bulgecin iminosaccharides and their mechanistic evaluation in a series of microbiological studies. These studies identify potentiation by the bulgecin at subminimum inhibitory concentrations of the β-lactam against three pathogenic Gram-negative bacteria and establish for the first time that this potentiation results in a significant increase in the bactericidal efficacy of a clinical β-lactam.
3. Structural studies and molecular dynamics simulations suggest a processive mechanism of exolytic lytic transglycosylase from Campylobacter jejuni
Jagamya Vijayaraghavan, Vijay Kumar, Nikhil P Krishnan, Ross T Kaufhold, Ximin Zeng, Jun Lin, Focco van den Akker PLoS One. 2018 May 14;13(5):e0197136. doi: 10.1371/journal.pone.0197136. eCollection 2018.
The bacterial soluble lytic transglycosylase (LT) breaks down the peptidoglycan (PG) layer during processes such as cell division. We present here crystal structures of the soluble LT Cj0843 from Campylobacter jejuni with and without bulgecin A inhibitor in the active site. Cj0843 has a doughnut shape similar but not identical to that of E. coli SLT70. The C-terminal catalytic domain is preceded by an L-domain, a large helical U-domain, a flexible linker, and a small N-terminal NU-domain. The flexible linker allows the NU-domain to reach over and complete the circular shape, using residues conserved in the Epsilonproteobacteria LT family. The inner surface of the Cj0843 doughnut is mostly positively charged including a pocket that has 8 Arg/Lys residues. Molecular dynamics simulations with PG strands revealed a potential functional role for this pocket in anchoring the negatively charged terminal tetrapeptide of the PG during several steps in the reaction including homing and aligning the PG strand for exolytic cleavage, and subsequent ratcheting of the PG strand to enhance processivity in degrading PG strands.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
