PDBsum entry 2rdk

Antiviral protein

PDB id: 2rdk

Contents

Protein chains

101 a.a. *

Ligands

MAN-MAN ×2

Waters ×259

* Residue conservation analysis

PDB id:

2rdk

Name:

Antiviral protein

Title:

Five site mutated cyanovirin-n with mannose dimer bound

Structure:

Cyanovirin-n. Chain: a, b. Synonym: cv-n. Engineered: yes. Mutation: yes

Source:

Nostoc ellipsosporum. Organism_taxid: 45916. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.35Å R-factor: 0.185 R-free: 0.199

Authors:

R.Fromme,Z.Katiliene,P.Fromme,G.Ghirlanda

Key ref:

R.Fromme et al. (2008). Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 A resolution. Protein Sci, 17, 939-944. PubMed id: 18436959 DOI: 10.1110/ps.083472808

Date:

24-Sep-07 Release date: 06-May-08

Protein chains

P81180  (CVN_NOSEL) -  Cyanovirin-N from Nostoc ellipsosporum

Seq: 101 a.a.

Struc: 101 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1110/ps.083472808

Protein Sci 17:939-944 (2008)

PubMed id: 18436959

Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 A resolution.

R.Fromme, Z.Katiliene, P.Fromme, G.Ghirlanda.

ABSTRACT

Cyanovirin (CV-N) is a small lectin with potent HIV neutralization activity, which could be exploited for a mucosal defense against HIV infection. The wild-type (wt) protein binds with high affinity to mannose-rich oligosaccharides on the surface of gp120 through two quasi-symmetric sites, located in domains A and B. We recently reported on a mutant of CV-N that contained a single functional mannose-binding site, domain B, showing that multivalent binding to oligomannosides is necessary for antiviral activity. The structure of the complex with dimannose determined at 1.8 A resolution revealed a different conformation of the binding site than previously observed in the NMR structure of wt CV-N. Here, we present the 1.35 A resolution structure of the complex, which traps three different binding conformations of the site and provides experimental support for a locking and gating mechanism in the nanoscale time regime observed by molecular dynamics simulations.

Selected figure(s)

Figure 1.
Crystal structure of P51G-m4-CVN at 1.35 A resolution: cartoon representation of one monomer in complex with dimannose. Domain A (green) contains four mutations (K3N, T7A, E23I, N93A, highlighted as red sticks) in the binding site, resulting in loss of binding (Chang and Bewley 2002). Domain B (blue) is unaltered and binds to dimannose. A P51G mutation in the hinge region stabilizes the monomer (Barrientos et al. 2002). The sequence of P51G-m4-CVN is reported below; domains A and B are represented in green and blue, respectively, while mutations from wt are in red. Figure generated with PyMOL (DeLano Scientific; http://www.pymol.org).

Figure 2.
Overlay of the backbone hinge region (residues 46 --57) of cyanovirin, monomer and dimer, and of P51G-m4-CVN. The monomeric NMR structure of wt CV-N (PDB code 2EZM) is represented in yellow, while the domain-swapped crystal structure (PDB code 1M5M) is represented in gray, and the monomeric crystal structure of P51G-m4-CVN in green (PDB code 2RDK; this work). Only the side chain of P51 (wt) is shown. In 2EZM, S52 assumes disallowed backbone dihedral angles.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2008, 17, 939-944) copyright 2008.

Figures were selected by an automated process.