Structural basis of the binding of fatty acids to peptidoglycan recognition protein, PGRP-S through second binding site

Pradeep Sharma, Shavait Yamini, Divya Dube, Amar Singh, Gorakh Mal, Nisha Pandey, Mau Sinha, Abhay Kumar Singh, Sharmistha Dey, Punit Kaur, Dipendra K. Mitra, Sujata Sharma, Tej P. Singh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume529
Issue number1
DOIs
StatePublished - Jan 1 2013

Bibliographical note

Funding Information:
The authors acknowledge financial support from the Department of Science and Technology (DST) , Ministry of Science and Technology, New Delhi . TPS thanks the Department of Biotechnology (DBT), Ministry of science and Technology, New Delhi for the award of Distinguished Biotechnology research professorship to him. PS thanks DST for INSPIRE-Faculty award to him. DD and MS thank DST for fellowships to them. SY and NP thank Council of Scientific and Industrial Research and Indian Council of Medical research, New Delhi respectively for the award of fellowships to them.

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • Binding constants
  • Crystal structure
  • Fatty acids
  • PGRP-S
  • Tuberculosis

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