3NG4

Ternary complex of peptidoglycan recognition protein (PGRP-S) with Maltose and N-Acetylglucosamine at 1.7 A Resolution

Summary for 3NG4

• Entry DOI: 10.2210/pdb3ng4/pdb
• Related: 2R2K 3C2X 3C93
• Related PRD ID: PRD_900001
• Descriptor: Peptidoglycan recognition protein 1, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, S,R MESO-TARTARIC ACID, ... (6 entities in total)
• Functional Keywords: antibiotic, peptidoglycan recognition protein, complex, nag, immune response, secreted, antimicrobial, immune system
• Biological source: Camelus dromedarius (Dromedary)
• Cellular location: Secreted (By similarity): Q9GK12
• Total number of polymer chains: 4
• Total formula weight: 76851.52

Authors

Sharma, P.,Dube, D.,Kaur, P.,Sharma, S.,Singh, T.P. (deposition date: 2010-06-10, release date: 2010-07-14, Last modification date: 2024-10-09)

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 (1.73 Å)