3umq
Crystal structure of peptidoglycan recognition protein-S complexed with butyric acid at 2.2 A resolution
Structural highlights
FunctionPGRP1_CAMDR Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Binds also to Gram-negative bacteria. Involved in innate immunity. Is microbicidal for Gram-positive and Gram-negative bacteria and yeast. May function in intracellular killing of bacteria (By similarity). Publication Abstract from PubMedShort peptidoglycan recognition protein (PGRP-S) is a member of the mammalian innate immune system. PGRP-S from Camelus dromedarius (CPGRP-S) has been shown to bind to lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN). Its structure consists of four molecules A, B, C and D with ligand binding clefts situated at A-B and C-D contacts. It has been shown that LPS, LTA and PGN bind to CPGRP-S at C-D contact. The cleft at the A-B contact indicated features that suggested a possible binding of fatty acids including mycolic acid of Mycobacterium tuberculosis. Therefore, binding studies of CPGRP-S were carried out with fatty acids, butyric acid, lauric acid, myristic acid, stearic acid and mycolic acid which showed affinities in the range of 10(-5) to 10(-8) M. Structure determinations of the complexes of CPGRP-S with above fatty acids showed that they bound to CPGRP-S in the cleft at the A-B contact. The flow cytometric studies showed that mycolic acid induced the production of pro-inflammatory cytokines, TNF-alpha and IFN-gamma by CD3+ T cells. The concentrations of cytokines increased considerably with increasing concentrations of mycolic acid. However, their levels decreased substantially on adding CPGRP-S. Structural basis of the binding of fatty acids to peptidoglycan recognition protein, PGRP-S through second binding site.,Sharma P, Yamini S, Dube D, Singh A, Mal G, Pandey N, Sinha M, Singh AK, Dey S, Kaur P, Mitra DK, Sharma S, Singh TP Arch Biochem Biophys. 2013 Jan 1;529(1):1-10. doi: 10.1016/j.abb.2012.11.001., Epub 2012 Nov 10. PMID:23149273[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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