3NW3

Crystal structure of the complex of peptidoglycan recognition protein (PGRP-S) with the PGN Fragment at 2.5 A resolution

Summary for 3NW3

• Entry DOI: 10.2210/pdb3nw3/pdb
• Descriptor: Peptidoglycan recognition protein 1, 2-acetamido-2-deoxy-alpha-D-glucopyranose, L(+)-TARTARIC ACID, ... (8 entities in total)
• Functional Keywords: immune response, secreted, antimicrobial, pgrp, antibiotic, peptidoglycan binding, immune system
• Biological source: Camelus dromedarius (dromedary)
• Total number of polymer chains: 4
• Total formula weight: 76834.54

Authors

Sharma, P.,Dube, D.,Sinha, M.,Kaur, P.,Sharma, S.,Singh, T.P. (deposition date: 2010-07-09, release date: 2010-08-04, Last modification date: 2023-11-15)

Primary citation

Sharma, P.,Dube, D.,Sinha, M.,Mishra, B.,Dey, S.,Mal, G.,Pathak, K.M.,Kaur, P.,Sharma, S.,Singh, T.P.
Multiligand specificity of pathogen-associated molecular pattern-binding site in peptidoglycan recognition protein
J.Biol.Chem., 286:31723-31730, 2011

PubMed 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 Å resolution and (ii) GlcNAc and β-maltose at 1.7Å 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 β-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-α 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 β-maltose revealed that MDP, GlcNAc, and β-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 β-maltose occupy distinct non-overlapping positions belonging to different subsites.

PubMed: 21784863
DOI: 10.1074/jbc.M111.264374

Experimental method

X-RAY DIFFRACTION (2.5 Å)