Structural studies and molecular dynamics simulations suggest a processive mechanism of exolytic lytic transglycosylase from Campylobacter jejuni
Abstract
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.
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
- OSTI Identifier:
- 1437092
- Alternate Identifier(s):
- OSTI ID: 1903987
- Grant/Contract Number:
- AC02-76SF00515; P41GM103393
- Resource Type:
- Published Article
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Name: PLoS ONE Journal Volume: 13 Journal Issue: 5; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science (PLoS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; atoms; disaccharides; hydrogen bonding; crystal structure; molecular dynamics; nitrogen; oxygen; boats
Citation Formats
Vijayaraghavan, Jagamya, Kumar, Vijay, Krishnan, Nikhil P., Kaufhold, Ross T., Zeng, Ximin, Lin, Jun, van den Akker, Focco, and Sticht, ed., Heinrich. Structural studies and molecular dynamics simulations suggest a processive mechanism of exolytic lytic transglycosylase from Campylobacter jejuni. United States: N. p., 2018.
Web. doi:10.1371/journal.pone.0197136.
Vijayaraghavan, Jagamya, Kumar, Vijay, Krishnan, Nikhil P., Kaufhold, Ross T., Zeng, Ximin, Lin, Jun, van den Akker, Focco, & Sticht, ed., Heinrich. Structural studies and molecular dynamics simulations suggest a processive mechanism of exolytic lytic transglycosylase from Campylobacter jejuni. United States. https://doi.org/10.1371/journal.pone.0197136
Vijayaraghavan, Jagamya, Kumar, Vijay, Krishnan, Nikhil P., Kaufhold, Ross T., Zeng, Ximin, Lin, Jun, van den Akker, Focco, and Sticht, ed., Heinrich. Mon .
"Structural studies and molecular dynamics simulations suggest a processive mechanism of exolytic lytic transglycosylase from Campylobacter jejuni". United States. https://doi.org/10.1371/journal.pone.0197136.
@article{osti_1437092,
title = {Structural studies and molecular dynamics simulations suggest a processive mechanism of exolytic lytic transglycosylase from Campylobacter jejuni},
author = {Vijayaraghavan, Jagamya and Kumar, Vijay and Krishnan, Nikhil P. and Kaufhold, Ross T. and Zeng, Ximin and Lin, Jun and van den Akker, Focco and Sticht, ed., Heinrich},
abstractNote = {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.},
doi = {10.1371/journal.pone.0197136},
journal = {PLoS ONE},
number = 5,
volume = 13,
place = {United States},
year = {Mon May 14 00:00:00 EDT 2018},
month = {Mon May 14 00:00:00 EDT 2018}
}
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