Int J Biochem Mol Biol 2012;3(1):86-94
Original Article
Structural basis of heparin binding to camel peptidoglycan recognition protein-S
Pradeep Sharma, Divya Dube, Mau Sinha, Sharmistha Dey, Punit Kaur, Sujata Sharma, Tej P Singh
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
Received February 8, 2012; accepted March 14, 2012; Epub March 20, 2012; Published March 30, 2012
Abstract: Short peptidoglycan recognition protein (PGRP-S) is a member of the innate immunity system in mammals. PGRP-S from Camelus
dromedarius (CPGRP-S) is found to be highly potent against bacterial infections. It is capable of binding to a wide range of pathogen-
associated molecular patterns (PAMPs) including lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN). The heparin-like
polysaccharides have also been observed in some bacteria such as the capsule of K5 Escherichia coli thus making them relevant for
determining the nature of their interactions with CPGRP-S. The binding studies of CPGRP-S with heparin disaccharide in solution using
surface plasmon resonance gave a value 3.3×10-7 M for the dissociation constant (Kd). The structure of the heparin bound CPGRP-S
determined at 2.8Å resolution revealed the presence of a bound heparin molecule in the binding pocket of CPGRP-S. It was found anchored
tightly to the protein with the help of several ionic and hydrogen bonded interactions. Three sulphate groups of heparin S1, S2 and S3 have
been found to interact with residues, Arg-31, Lys-90, Thr-97, Asn-99 Asn-140, Gln-150 and Arg-170 of CPGRP-S. The binding site includes two
subsites, S-I and S-II with cleft-like structures. Heparin disaccharide is bound in subsite S-I. Previously determined structures of the complexes
of CPGRP-S with LPS, LTA and PGN also showed that their glycan moieties were also held in subsite S-I indicating that heparin disaccharide
also represents an important element for the recognition by CPGRP-S. (IJBMB1202001).
Keywords: PGRP-S, PAMPs, heparin, crystal structure, LPS, LTA, PGN
Address all correspondence to:
Dr. Singh TP
Department of Biophysics
All India Institute of Medical Sciences
Ansari Nagar, New Delhi – 110 029, India
Tel: +91-11-2658-8931; Fax: +91-11-2658-8663
E-mail: tpsingh.aiims@gmail.com
Original Article
Structural basis of heparin binding to camel peptidoglycan recognition protein-S
Pradeep Sharma, Divya Dube, Mau Sinha, Sharmistha Dey, Punit Kaur, Sujata Sharma, Tej P Singh
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
Received February 8, 2012; accepted March 14, 2012; Epub March 20, 2012; Published March 30, 2012
Abstract: Short peptidoglycan recognition protein (PGRP-S) is a member of the innate immunity system in mammals. PGRP-S from Camelus
dromedarius (CPGRP-S) is found to be highly potent against bacterial infections. It is capable of binding to a wide range of pathogen-
associated molecular patterns (PAMPs) including lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN). The heparin-like
polysaccharides have also been observed in some bacteria such as the capsule of K5 Escherichia coli thus making them relevant for
determining the nature of their interactions with CPGRP-S. The binding studies of CPGRP-S with heparin disaccharide in solution using
surface plasmon resonance gave a value 3.3×10-7 M for the dissociation constant (Kd). The structure of the heparin bound CPGRP-S
determined at 2.8Å resolution revealed the presence of a bound heparin molecule in the binding pocket of CPGRP-S. It was found anchored
tightly to the protein with the help of several ionic and hydrogen bonded interactions. Three sulphate groups of heparin S1, S2 and S3 have
been found to interact with residues, Arg-31, Lys-90, Thr-97, Asn-99 Asn-140, Gln-150 and Arg-170 of CPGRP-S. The binding site includes two
subsites, S-I and S-II with cleft-like structures. Heparin disaccharide is bound in subsite S-I. Previously determined structures of the complexes
of CPGRP-S with LPS, LTA and PGN also showed that their glycan moieties were also held in subsite S-I indicating that heparin disaccharide
also represents an important element for the recognition by CPGRP-S. (IJBMB1202001).
Keywords: PGRP-S, PAMPs, heparin, crystal structure, LPS, LTA, PGN
Address all correspondence to:
Dr. Singh TP
Department of Biophysics
All India Institute of Medical Sciences
Ansari Nagar, New Delhi – 110 029, India
Tel: +91-11-2658-8931; Fax: +91-11-2658-8663
E-mail: tpsingh.aiims@gmail.com
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