3O4K

Crystal structure of the complex of peptidoglycan recognition protein (PGRP-S) and lipoteichoic acid at 2.1 A resolution

Summary for 3O4K

• Entry DOI: 10.2210/pdb3o4k/pdb
• Descriptor: Peptidoglycan recognition protein 1, (2S)-1-({3-O-[2-(acetylamino)-4-amino-2,4,6-trideoxy-beta-D-galactopyranosyl]-alpha-D-glucopyranosyl}oxy)-3-(heptanoyloxy)propan-2-yl (7Z)-pentadec-7-enoate, GLYCEROL, ... (5 entities in total)
• Functional Keywords: immune response, secreted, antimicrobial, pgrp, antibiotic, peptidoglycan binding, immune system
• Biological source: Camelus dromedarius (dromedary)
• Cellular location: Secreted (By similarity): Q9GK12
• Total number of polymer chains: 4
• Total formula weight: 77063.00

Authors

Sharma, P.,Dube, D.,Sinha, M.,Kaur, P.,Sharma, S.,Singh, T.P. (deposition date: 2010-07-27, release date: 2010-08-25, Last modification date: 2024-11-20)

Primary citation

Sharma, P.,Dube, D.,Singh, A.,Mishra, B.,Singh, N.,Sinha, M.,Dey, S.,Kaur, P.,Mitra, D.K.,Sharma, S.,Singh, T.P.
Structural basis of recognition of pathogen-associated molecular patterns and inhibition of proinflammatory cytokines by camel peptidoglycan recognition protein
J.Biol.Chem., 286:16208-16217, 2011

PubMed Abstract: Peptidoglycan recognition proteins (PGRPs) are involved in the recognition of pathogen-associated molecular patterns. The well known pathogen-associated molecular patterns include LPS from Gram-negative bacteria and lipoteichoic acid (LTA) from Gram-positive bacteria. In this work, the crystal structures of two complexes of the short form of camel PGRP (CPGRP-S) with LPS and LTA determined at 1.7- and 2.1-Å resolutions, respectively, are reported. Both compounds were held firmly inside the complex formed with four CPGRP-S molecules designated A, B, C, and D. The binding cleft is located at the interface of molecules C and D, which is extendable to the interface of molecules A and C. The interface of molecules A and B is tightly packed, whereas that of molecules B and D forms a wide channel. The hydrophilic moieties of these compounds occupy a common region, whereas hydrophobic chains interact with distinct regions in the binding site. The binding studies showed that CPGRP-S binds to LPS and LTA with affinities of 1.6 × 10(-9) and 2.4 × 10(-8) M, respectively. The flow cytometric studies showed that both LPS- and LTA-induced expression of the proinflammatory cytokines TNF-α and IL-6 was inhibited by CPGRP-S. The results of animal studies using mouse models indicated that both LPS- and LTA-induced mortality rates decreased drastically when CPGRP-S was administered. The recognition of both LPS and LTA, their high binding affinities for CPGRP-S, the significant decrease in the production of LPS- and LTA-induced TNF-α and IL-6, and the drastic reduction in the mortality rates in mice by CPGRP-S indicate its useful properties as an antibiotic agent.

PubMed: 21454594
DOI: 10.1074/jbc.M111.228163

Experimental method

X-RAY DIFFRACTION (2.11 Å)