 |
PDBsum entry 1zhs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sugar binding protein
|
PDB id
|
|
|
|
1zhs
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
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.
|
|
|
Authors
|
|
D.C.Williams,
J.Y.Lee,
M.Cai,
C.A.Bewley,
G.M.Clore.
|
|
|
Ref.
|
|
J Biol Chem, 2005,
280,
29269-29276.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
