title: Structural basis of the binding of fatty acids to peptidoglycan recognition protein, PGRP-S through second binding site.
abstract: Short 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-α and IFN-γ 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.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sharma
authors.forename: Shavait
authors.initials: S
authors.lastname: Yamini
authors.forename: Divya
authors.initials: D
authors.lastname: Dube
authors.forename: Amar
authors.initials: A
authors.lastname: Singh
authors.forename: Gorakh
authors.initials: G
authors.lastname: Mal
authors.forename: Nisha
authors.initials: N
authors.lastname: Pandey
authors.forename: Mau
authors.initials: M
authors.lastname: Sinha
authors.forename: Abhay Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Dey
authors.forename: Punit
authors.initials: P
authors.lastname: Kaur
authors.forename: Dipendra K
authors.initials: DK
authors.lastname: Mitra
authors.forename: Sujata
authors.initials: S
authors.lastname: Sharma
authors.forename: Tej P
authors.initials: TP
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020148:Butyric Acid / Q000737:chemistry; D002162:Camelus; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007700:Kinetics; D007850:Lauric Acids / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D008321:Mammary Glands, Animal / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry; D009171:Mycolic Acids / Q000737:chemistry* / Q000494:pharmacology; D019814:Myristic Acid / Q000737:chemistry; D010457:Peptidoglycan / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013229:Stearic Acids / Q000737:chemistry; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013682:Teichoic Acids / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D002352:Carrier Proteins; D007850:Lauric Acids; D008070:Lipopolysaccharides; D009171:Mycolic Acids; D010457:Peptidoglycan; D013229:Stearic Acids; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C118897:peptidoglycan recognition protein; D019814:Myristic Acid; D020148:Butyric Acid; C030358:lauric acid; C031183:stearic acid; C009900:lipoteichoic acid; D007371:Interferon-gamma