TY  - JOUR
AU  - Leysen, S.
AU  - Vanderkelen, L.
AU  - Weeks, S. D.
AU  - Michiels, C. W.
AU  - Strelkov, S. V.
AU  - DESY
TI  - Structural basis of bacterial defense against g-type lysozyme-based innate immunity
JO  - Cellular and molecular life sciences
VL  - 70
SN  - 1420-682X
CY  - Basel
PB  - Birkhäuser
M1  - PHPPUBDB-25506
SP  - 1-10
PY  - 2013
N1  - © Springer Basel; Post referee fulltext in progress; Embargo 12 months from publication 
AB  - Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double 'key-lock' mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG.
KW  - Animals
KW  - Crystallography
KW  - Escherichia coli: chemistry
KW  - Escherichia coli: immunology
KW  - Escherichia coli Proteins: chemistry
KW  - Escherichia coli Proteins: metabolism
KW  - Immunity, Innate: immunology
KW  - Models, Molecular
KW  - Muramidase: chemistry
KW  - Muramidase: metabolism
KW  - Protein Conformation
KW  - Salmo salar
KW  - Escherichia coli Proteins (NLM Chemicals)
KW  - PliG protein, E coli (NLM Chemicals)
KW  - Muramidase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23086131
UR  - <Go to ISI:>//WOS:000315343600011
DO  - DOI:10.1007/s00018-012-1184-1
UR  - https://bib-pubdb1.desy.de/record/142547
ER  -