3NW3: Crystal Structure Of The Complex Of Peptidoglycan Recognition Protein (Pgrp-S) With The Pgn Fragment At 2.5 A Resolution

Citation:
Abstract
The peptidoglycan recognition protein PGRP-S is an innate immunity molecule that specifically interacts with microbial peptidoglycans and other pathogen-associated molecular patterns. We report here two structures of the unique tetrameric camel PGRP-S (CPGRP-S) complexed with (i) muramyl dipeptide (MDP) at 2.5 A resolution and (ii) GlcNAc and beta-maltose at 1.7A resolution. The binding studies carried out using surface plasmon resonance indicated that CPGRP-S binds to MDP with a dissociation constant of 10(-7) M, whereas the binding affinities for GlcNAc and beta-maltose separately are in the range of 10(-4) M to 10(-5) M, whereas the dissociation constant for the mixture of GlcNAc and maltose was estimated to be 10(-6) M. The data from bacterial suspension culture experiments showed a significant inhibition of the growth of Staphylococcus aureus cells when CPGRP-S was added to culture medium. The ELISA experiment showed that the amount of MDP-induced production of TNF-alpha and IL-6 decreased considerably after the introduction of CPGRP-S. The crystal structure determinations of (i) a binary complex with MDP and (ii) a ternary complex with GlcNAc and beta-maltose revealed that MDP, GlcNAc, and beta-maltose bound to CPGRP-S in the ligand binding cleft, which is situated at the interface of molecules C and D of the homotetramer formed by four protein molecules A, B, C, and D. In the binary complex, the muramyl moiety of MDP is observed at the C-D interface, whereas the peptide chain protrudes into the center of tetramer. In the ternary complex, GlcNAc and beta-maltose occupy distinct non-overlapping positions belonging to different subsites.
PDB ID: 3NW3Download
MMDB ID: 83879
PDB Deposition Date: 2010/7/9
Updated in MMDB: 2010/08
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Similar Structures:
Biological Unit for 3NW3: tetrameric; determined by author
Molecular Components in 3NW3
Label Count Molecule
Proteins (4 molecules)
4
Peptidoglycan Recognition Protein 1
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

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