PDBsum entry 4c1w

Sugar binding protein

PDB id: 4c1w

Contents

Protein chain

188 a.a.

Ligands

GLC-GAL-SIA

TRS

Waters ×170

PDB id:

4c1w

Name:

Sugar binding protein

Title:

Carbohydrate binding domain from streptococcus pneumoniae nana sialidase complexed with 3'-sialyllactose

Structure:

Neuraminidase. Chain: a. Fragment: cbm40, residues 52-236. Engineered: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Strain: r36a / nctc 10319. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.84Å R-factor: 0.145 R-free: 0.198

Authors:

L.Yang,H.Connaris,J.A.Potter,G.L.Taylor

Key ref:

H.Connaris et al. (2014). Prevention of influenza by targeting host receptors using engineered proteins. Proc Natl Acad Sci U S A, 111, 6401-6406. PubMed id: 24733924 DOI: 10.1073/pnas.1404205111

Date:

14-Aug-13 Release date: 27-Aug-14

Protein chain

Q4LB86  (Q4LB86_STREE) -  exo-alpha-sialidase (Fragment) from Streptococcus pneumoniae

Seq: 672 a.a.

Struc: 188 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.1.18 - exo-alpha-sialidase.
• Reaction: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)-glycosidic linkages of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.

DOI no: 10.1073/pnas.1404205111

Proc Natl Acad Sci U S A 111:6401-6406 (2014)

PubMed id: 24733924

Prevention of influenza by targeting host receptors using engineered proteins.

H.Connaris, E.A.Govorkova, Y.Ligertwood, B.M.Dutia, L.Yang, S.Tauber, M.A.Taylor, N.Alias, R.Hagan, A.A.Nash, R.G.Webster, G.L.Taylor.

ABSTRACT

There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. We show that multivalent biologics, engineered using carbohydrate-binding modules specific for sialic acid, mask the cell-surface receptor recognized by the influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1 influenza virus. The most promising biologic protects mice when given as a single 1-μg intranasal dose 7 d in advance of viral challenge. There also is sufficient virus replication to establish an immune response, potentially protecting the animal from future exposure to the virus. Furthermore, the biologics appear to stimulate inflammatory mediators, and this stimulation may contribute to their protective ability. Our results suggest that this host-targeted approach could provide a front-line prophylactic that has the potential to protect against any current and future influenza virus and possibly against other respiratory pathogens that use sialic acid as a receptor.