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* Residue conservation analysis
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Enzyme class:
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E.C.3.4.17.13
- Muramoyltetrapeptide carboxypeptidase.
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Reaction:
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GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelyl-D-alanine + H2O = GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelate + D-alanine
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GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelyl-D-alanine
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+
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H(2)O
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=
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GlcNAc-MurNAc-L-alanyl-gamma-D-glutamyl-meso-diaminopimelate
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+
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D-alanine
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Biological process
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peptidoglycan catabolic process
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1 term
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Biochemical function
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protein binding
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2 terms
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DOI no:
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Plos Biol
2:E277-1302
(2004)
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PubMed id:
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A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity.
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C.I.Chang,
S.Pili-Floury,
M.Hervé,
C.Parquet,
Y.Chelliah,
B.Lemaitre,
D.Mengin-Lecreulx,
J.Deisenhofer.
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ABSTRACT
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The Drosophila peptidoglycan recognition protein SA (PGRP-SA) is critically
involved in sensing bacterial infection and activating the Toll signaling
pathway, which induces the expression of specific antimicrobial peptide genes.
We have determined the crystal structure of PGRP-SA to 2.2-A resolution and
analyzed its peptidoglycan (PG) recognition and signaling activities. We found
an extended surface groove in the structure of PGRP-SA, lined with residues that
are highly diverse among different PGRPs. Mutational analysis identified it as a
PG docking groove required for Toll signaling and showed that residue Ser158 is
essential for both PG binding and Toll activation. Contrary to the general
belief that PGRP-SA has lost enzyme function and serves primarily for PG
sensing, we found that it possesses an intrinsic L,D-carboxypeptidase activity
for diaminopimelic acid-type tetrapeptide PG fragments but not lysine-type PG
fragments, and that Ser158 and His42 may participate in the hydrolytic activity.
As L,D-configured peptide bonds exist only in prokaryotes, this work reveals a
rare enzymatic activity in a eukaryotic protein known for sensing bacteria and
provides a possible explanation of how PGRP-SA mediates Toll activation
specifically in response to lysine-type PG.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.M.Montaño,
F.Tsujino,
N.Takahata,
and
Y.Satta
(2011).
Evolutionary origin of peptidoglycan recognition proteins in vertebrate innate immune system.
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BMC Evol Biol, 11,
79.
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N.T.Nehme,
J.Quintin,
J.H.Cho,
J.Lee,
M.C.Lafarge,
C.Kocks,
and
D.Ferrandon
(2011).
Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.
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PLoS One, 6,
e14743.
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S.Meister,
B.Agianian,
F.Turlure,
A.Relógio,
I.Morlais,
F.C.Kafatos,
and
G.K.Christophides
(2009).
Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
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PLoS Pathog, 5,
e1000542.
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Y.Mishima,
J.Quintin,
V.Aimanianda,
C.Kellenberger,
F.Coste,
C.Clavaud,
C.Hetru,
J.A.Hoffmann,
J.P.Latgé,
D.Ferrandon,
and
A.Roussel
(2009).
The N-terminal domain of Drosophila Gram-negative binding protein 3 (GNBP3) defines a novel family of fungal pattern recognition receptors.
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J Biol Chem, 284,
28687-28697.
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PDB code:
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B.Lemaitre,
and
J.Hoffmann
(2007).
The host defense of Drosophila melanogaster.
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Annu Rev Immunol, 25,
697-743.
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D.Ferrandon,
J.L.Imler,
C.Hetru,
and
J.A.Hoffmann
(2007).
The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections.
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Nat Rev Immunol, 7,
862-874.
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J.Royet,
and
R.Dziarski
(2007).
Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences.
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Nat Rev Microbiol, 5,
264-277.
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J.W.Park,
C.H.Kim,
J.H.Kim,
B.R.Je,
K.B.Roh,
S.J.Kim,
H.H.Lee,
J.H.Ryu,
J.H.Lim,
B.H.Oh,
W.J.Lee,
N.C.Ha,
and
B.L.Lee
(2007).
Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects.
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Proc Natl Acad Sci U S A, 104,
6602-6607.
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M.Firczuk,
and
M.Bochtler
(2007).
Folds and activities of peptidoglycan amidases.
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FEMS Microbiol Rev, 31,
676-691.
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R.Guan,
and
R.A.Mariuzza
(2007).
Peptidoglycan recognition proteins of the innate immune system.
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Trends Microbiol, 15,
127-134.
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C.I.Chang,
Y.Chelliah,
D.Borek,
D.Mengin-Lecreulx,
and
J.Deisenhofer
(2006).
Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor.
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Science, 311,
1761-1764.
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PDB code:
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L.S.Garver,
J.Wu,
and
L.P.Wu
(2006).
The peptidoglycan recognition protein PGRP-SC1a is essential for Toll signaling and phagocytosis of Staphylococcus aureus in Drosophila.
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Proc Natl Acad Sci U S A, 103,
660-665.
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L.Wang,
A.N.Weber,
M.L.Atilano,
S.R.Filipe,
N.J.Gay,
and
P.Ligoxygakis
(2006).
Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA.
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EMBO J, 25,
5005-5014.
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R.Dziarski,
and
D.Gupta
(2006).
The peptidoglycan recognition proteins (PGRPs).
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Genome Biol, 7,
232.
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C.I.Chang,
K.Ihara,
Y.Chelliah,
D.Mengin-Lecreulx,
S.Wakatsuki,
and
J.Deisenhofer
(2005).
Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition.
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Proc Natl Acad Sci U S A, 102,
10279-10284.
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PDB code:
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H.J.Korza,
and
M.Bochtler
(2005).
Pseudomonas aeruginosa LD-carboxypeptidase, a serine peptidase with a Ser-His-Glu triad and a nucleophilic elbow.
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J Biol Chem, 280,
40802-40812.
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PDB codes:
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J.Royet,
J.M.Reichhart,
and
J.A.Hoffmann
(2005).
Sensing and signaling during infection in Drosophila.
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Curr Opin Immunol, 17,
11-17.
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P.Mellroth,
J.Karlsson,
J.Håkansson,
N.Schultz,
W.E.Goldman,
and
H.Steiner
(2005).
Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in vitro.
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Proc Natl Acad Sci U S A, 102,
6455-6460.
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T.Kaneko,
and
N.Silverman
(2005).
Bacterial recognition and signalling by the Drosophila IMD pathway.
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Cell Microbiol, 7,
461-469.
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Y.Sang,
B.Ramanathan,
C.R.Ross,
and
F.Blecha
(2005).
Gene silencing and overexpression of porcine peptidoglycan recognition protein long isoforms: involvement in beta-defensin-1 expression.
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Infect Immun, 73,
7133-7141.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
