PDBsum entry 2ric

Sugar binding protein

PDB id: 2ric

Contents

Protein chain

155 a.a. *

Ligands

GMH-GMH ×2

GMH

Metals

_CA ×9

Waters ×427

* Residue conservation analysis

PDB id:

2ric

Name:

Sugar binding protein

Title:

Crystal structure of the trimeric neck and carbohydrate recognition domain of human surfactant protein d in complex with l-glycero-d- manno-heptopyranosyl-(1-3)-l-glycero-d-manno-heptopyranose

Structure:

Pulmonary surfactant-associated protein d. Chain: a, b, c. Fragment: neck and carbohydrate recognition domain. Synonym: sp-d. Psp-d. Lung surfactant protein d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sftpd, pspd, sftp4. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.205 R-free: 0.230

Authors:

H.Wang,J.Head,P.Kosma,S.Sheikh,B.Mcdonald,K.Smith,T.Cafarella, B.Seaton,E.Crouch

Key ref:

H.Wang et al. (2008). Recognition of heptoses and the inner core of bacterial lipopolysaccharides by surfactant protein d. Biochemistry, 47, 710-720. PubMed id: 18092821

Date:

10-Oct-07 Release date: 15-Jan-08

Protein chains

P35247  (SFTPD_HUMAN) -  Pulmonary surfactant-associated protein D from Homo sapiens

Seq: 375 a.a.

Struc: 155 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Biochemistry 47:710-720 (2008)

PubMed id: 18092821

Recognition of heptoses and the inner core of bacterial lipopolysaccharides by surfactant protein d.

H.Wang, J.Head, P.Kosma, H.Brade, S.Müller-Loennies, S.Sheikh, B.McDonald, K.Smith, T.Cafarella, B.Seaton, E.Crouch.

ABSTRACT

Lipopolysaccharides (LPS) of Gram-negative bacteria are important mediators of bacterial virulence that can elicit potent endotoxic effects. Surfactant protein D (SP-D) shows specific interactions with LPS, both in vitro and in vivo. These interactions involve binding of the carbohydrate recognition domain (CRD) to LPS oligosaccharides (OS); however, little is known about the mechanisms of LPS recognition. Recombinant neck+CRDs (NCRDs) provide an opportunity to directly correlate binding interactions with a crystallographic analysis of the binding mechanism. In these studies, we examined the interactions of wild-type and mutant trimeric NCRDs with rough LPS (R-LPS). Although rat NCRDs bound more efficiently than human NCRDs to Escherichia coli J-5 LPS, both proteins exhibited efficient binding to solid-phase Rd2-LPS and to Rd2-LPS aggregates presented in the solution phase. Involvement of residues flanking calcium at the sugar binding site was demonstrated by reciprocal exchange of lysine and arginine at position 343 of rat and human CRDs. The lectin activity of hNCRDs was inhibited by specific heptoses, including l-glycero-alpha-d-manno-heptose (l,d-heptose), but not by 3-deoxy-alpha-d-manno-oct-2-ulosonic acid (Kdo). Crystallographic analysis of the hNCRD demonstrated a novel binding orientation for l,d-heptose, involving the hydroxyl groups of the side chain. Similar binding was observed for a synthetic alpha1-->3-linked heptose disaccharide corresponding to heptoses I and II of the inner core region in many LPS. 7-O-Carbamoyl-l,d-heptose and d-glycero-alpha-d-manno-heptose were bound via ring hydroxyl groups. Interactions with the side chain of inner core heptoses provide a potential mechanism for the recognition of diverse types of LPS by SP-D.