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PDBsum entry 1e8v

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Hydrolase PDB id
1e8v
Jmol
Contents
Protein chains
447 a.a. *
Ligands
DAN ×2
NAG ×3
NAG-NAG
Metals
_CA ×2
Waters ×239
* Residue conservation analysis

References listed in PDB file
Key reference
Title Crystal structure of the multifunctional paramyxovirus hemagglutinin-Neuraminidase.
Authors S.Crennell, T.Takimoto, A.Portner, G.Taylor.
Ref. Nat Struct Biol, 2000, 7, 1068-1074. [DOI no: 10.1038/81002]
PubMed id 11062565
Abstract
Paramyxoviruses are the main cause of respiratory disease in children. One of two viral surface glycoproteins, the hemagglutinin-neuraminidase (HN), has several functions in addition to being the major surface antigen that induces neutralizing antibodies. Here we present the crystal structures of Newcastle disease virus HN alone and in complex with either an inhibitor or with the beta-anomer of sialic acid. The inhibitor complex reveals a typical neuraminidase active site within a beta-propeller fold. Comparison of the structures of the two complexes reveal differences in the active site, suggesting that the catalytic site is activated by a conformational switch. This site may provide both sialic acid binding and hydrolysis functions since there is no evidence for a second sialic acid binding site in HN. Evidence for a single site with dual functions is examined and supported by mutagenesis studies. The structure provides the basis for the structure-based design of inhibitors for a range of paramyxovirus-induced diseases.
Figure 1.
Figure 1. Schematic representations of the crystal structure of HN. The chains are colored from blue at the N-terminus through to red at the C-terminus. The N-linked carbohydrate residues are shown in ball and stick representation, and the divalent metal ions are drawn as gray spheres. a, The HN dimer observed in the orthorhombic crystal form, viewed down the NCS two-fold axis showing the location of the -anomer of sialic acid drawn as a space filling molecule. b, The dimer of the HN -Neu5Ac2en complex observed in the hexagonal crystal form, viewed down the NCS two-fold axis. c, The image in (b) rotated by 45 around a horizontal axis and colored according to B-factor conveniently reveals orthogonal views of the HN monomer. Coloring is from dark blue (B = 10 2) to deep red (B = 60 2).
Figure 3.
Figure 3. The active site. a, The inhibitor Neu5Ac2en bound in the active site of the hexagonal crystal form. b, The same active site as observed in the ligand-free pH 4.6 orthorhombic crystal structure. c, The -anomer of sialic acid bound in the active site of the pH 4.6 orthorhombic crystal form, showing hydrogen bonding interactions (dotted lines). Water molecules are labeled W.
The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 1068-1074) copyright 2000.
Secondary reference #1
Title Crystallization of newcastle disease virus hemagglutinin-Neuraminidase glycoprotein.
Authors T.Takimoto, G.L.Taylor, S.J.Crennell, R.A.Scroggs, A.Portner.
Ref. Virology, 2000, 270, 208-214. [DOI no: 10.1006/viro.2000.0263]
PubMed id 10772993
Abstract
PROCHECK
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