PDBsum entry 1zhs

Sugar binding protein

PDB id: 1zhs

Contents

Protein chains

(+ 2 more) 113 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN ×16

EDO ×26

PO4 ×2

Waters ×643

PDB id:

1zhs

Name:

Sugar binding protein

Title:

Crystal structure of mvl bound to man3glcnac2

Structure:

Mannan-binding lectin. Chain: a, b, c, d, e, f, g, h. Synonym: mvl. Engineered: yes

Source:

Microcystis viridis. Organism_taxid: 44822. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Octamer (from PQS)

Resolution:

1.80Å R-factor: 0.192 R-free: 0.221

Authors:

D.C.Williams,J.Y.Lee,M.Cai,C.A.Bewley,G.M.Clore

Key ref:

D.C.Williams et al. (2005). Crystal structures of the HIV-1 inhibitory cyanobacterial protein MVL free and bound to Man3GlcNAc2: structural basis for specificity and high-affinity binding to the core pentasaccharide from n-linked oligomannoside. J Biol Chem, 280, 29269-29276. PubMed id: 15937331 DOI: 10.1074/jbc.M504642200

Date:

26-Apr-05 Release date: 07-Jun-05

Protein chains

Q9RHG4  (MVL_MICVR) -  Lectin MVL from Microcystis viridis

Seq: 114 a.a.

Struc: 113 a.a.

Enzyme reactions

• Enzyme class: E.C.3.2.1.- - ?????

DOI no: 10.1074/jbc.M504642200

J Biol Chem 280:29269-29276 (2005)

PubMed id: 15937331

Crystal structures of the HIV-1 inhibitory cyanobacterial protein MVL free and bound to Man3GlcNAc2: structural basis for specificity and high-affinity binding to the core pentasaccharide from n-linked oligomannoside.

D.C.Williams, J.Y.Lee, M.Cai, C.A.Bewley, G.M.Clore.

ABSTRACT

The cyanobacterial protein MVL inhibits HIV-1 envelope-mediated cell fusion at nanomolar concentrations by binding to high mannose N-linked carbohydrate on the surface of the envelope glycoprotein gp120. Although a number of other carbohydrate-binding proteins have been shown to inhibit HIV-1 envelope-mediated cell fusion, the specificity of MVL is unique in that its minimal target comprises the Man(alpha)(1-->6)Man(beta)(1-->4)GlcNAc(beta)(1-->4)GlcNAc tetrasaccharide core of oligomannosides. We have solved the crystal structures of MVL free and bound to the pentasaccharide Man3GlcNAc2 at 1.9- and 1.8-A resolution, respectively. MVL is a homodimer stabilized by an extensive intermolecular interface between monomers. Each monomer contains two structurally homologous domains with high sequence similarity connected by a short five-amino acid residue linker. Intriguingly, a water-filled channel is observed between the two monomers. Residual dipolar coupling measurements indicate that the structure of the MVL dimer in solution is identical to that in the crystal. Man3GlcNAc2 binds to a preformed cleft at the distal end of each domain such that a total of four independent carbohydrate molecules associate with each homodimer. The binding cleft provides shape complementarity, including the presence of a deep hydrophobic hole that accommodates the N-acetyl methyl at the reducing end of the carbohydrate, and specificity arises from 7-8 intermolecular hydrogen bonds. The structures of MVL and the MVL-Man3GlcNAc2 complex further our understanding of the molecular basis of high affinity and specificity in protein-carbohydrate recognition.

Selected figure(s)

Figure 2.
FIG. 2. Comparison of the carbohydrate binding pockets in MVL free and complexed to Man[3]GlcNAc[2]. The backbone of the binding pocket and side chains involved in protein-carbohydrate hydrogen-bonding interactions is displayed, and each panel shows a best-fit superposition of the eight MVL monomers in the asymmetric unit in the free and bound states. A, N-domain; B, C-domain. Free MVL, red; complexed MVL, blue; Man[3]GlcNAc[2] (one of the eight molecules bound to each domain), yellow, with oxygen atoms in red and nitrogen atoms in blue. Note that the O-6 hydroxyl group of the Man4 unit is hydrogen-bonded to the hydroxyl group of Thr-38 in the N-domain pocket (A); in the C-domain pocket (B) the equivalent residue is Arg-97, and hence no such hydrogen bond can be formed. This difference leads to a 180° rotation about the O-5-C-5-C-6-O-6 dihedral angle of Man4 such that the C-6-O-6 bond points in the opposite direction in the N- and C-domain pockets.

Figure 4.
FIG. 4. Schematic diagram of hydrogen-bonding interactions between MVL and Man[3]GlcNAc[2]. The carbohydrate structure is shown in red and the contacting protein residues in black. Dashed lines indicate hydrogen bonds, and the dashed arcs represent hydrophobic contacts.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 29269-29276) copyright 2005.

Figures were selected by an automated process.