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Title: An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

Abstract

The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

Authors:
 [1];  [2]; ; ;  [3]; ; ;  [2]
  1. University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark)
  2. Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)
  3. University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark)
Publication Date:
OSTI Identifier:
22347724
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography
Additional Journal Information:
Journal Volume: 71; Journal Issue: Pt 3; Other Information: PMCID: PMC4356369; PMID: 25760608; PUBLISHER-ID: rr5089; OAI: oai:pubmedcentral.nih.gov:4356369; Copyright (c) Wong et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0907-4449
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CRYSTAL STRUCTURE; CRYSTALS; DIMERIZATION; INTERACTIONS; LIGANDS; MATHEMATICAL SOLUTIONS; RESOLUTION; SCATTERING; SOLUTIONS; SUBSTRATES

Citation Formats

Wong, Jaslyn E. M. M., Midtgaard, Søren Roi, Gysel, Kira, Thygesen, Mikkel B., Sørensen, Kasper K., Jensen, Knud J., Stougaard, Jens, Thirup, Søren, and Blaise, Mickaël. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase. Denmark: N. p., 2015. Web. doi:10.1107/S139900471402793X.
Wong, Jaslyn E. M. M., Midtgaard, Søren Roi, Gysel, Kira, Thygesen, Mikkel B., Sørensen, Kasper K., Jensen, Knud J., Stougaard, Jens, Thirup, Søren, & Blaise, Mickaël. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase. Denmark. doi:10.1107/S139900471402793X.
Wong, Jaslyn E. M. M., Midtgaard, Søren Roi, Gysel, Kira, Thygesen, Mikkel B., Sørensen, Kasper K., Jensen, Knud J., Stougaard, Jens, Thirup, Søren, and Blaise, Mickaël. Sun . "An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase". Denmark. doi:10.1107/S139900471402793X.
@article{osti_22347724,
title = {An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase},
author = {Wong, Jaslyn E. M. M. and Midtgaard, Søren Roi and Gysel, Kira and Thygesen, Mikkel B. and Sørensen, Kasper K. and Jensen, Knud J. and Stougaard, Jens and Thirup, Søren and Blaise, Mickaël},
abstractNote = {The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.},
doi = {10.1107/S139900471402793X},
journal = {Acta Crystallographica. Section D: Biological Crystallography},
issn = {0907-4449},
number = Pt 3,
volume = 71,
place = {Denmark},
year = {2015},
month = {3}
}