PDBsum entry 1flc

Hydrolase

PDB id: 1flc

Contents

Protein chains

427 a.a. *

162 a.a. *

Ligands

NAG-NAG-BMA ×11

NAG-NDG-MAN ×3

NAG-NDG-BMA

* Residue conservation analysis

PDB id:

1flc

Name:

Hydrolase

Title:

X-ray structure of the haemagglutinin-esterase-fusion glycoprotein of influenza c virus

Structure:

Haemagglutinin-esterase-fusion glycoprotein. Chain: a, c, e. Fragment: hef1. Engineered: yes. Haemagglutinin-esterase-fusion glycoprotein. Chain: b, d, f. Fragment: hef2. Engineered: yes

Source:

Influenza c virus (c/johannesburg/1/66). Organism_taxid: 100673. Strain: c/johannesburg/1/66. Strain: c/johannesburg/1/66

Biol. unit:

Hexamer (from PQS)

Resolution:

3.20Å R-factor: 0.223 R-free: 0.267

Authors:

P.B.Rosenthal,X.Zhang,F.Formanowski,W.Fitz,C.H.Wong,H.Meier-Ewert, J.J.Skehel,D.C.Wiley

Key ref:

P.B.Rosenthal et al. (1998). Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus. Nature, 396, 92-96. PubMed id: 9817207 DOI: 10.1038/23974

Date:

22-Feb-99 Release date: 01-Mar-00

Protein chains

P07975  (HEMA_INCJH) -  Hemagglutinin-esterase-fusion glycoprotein from Influenza C virus (strain C/Johannesburg/1/1966)

Seq: 655 a.a.

Struc: 427 a.a.

Protein chains

P07975  (HEMA_INCJH) -  Hemagglutinin-esterase-fusion glycoprotein from Influenza C virus (strain C/Johannesburg/1/1966)

Seq: 655 a.a.

Struc: 162 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F: E.C.3.1.1.53 - sialate O-acetylesterase.
• Reaction:
  1. N-acetyl-9-O-acetylneuraminate + H2O = N-acetylneuraminate + acetate + H⁺
  2. N-acetyl-4-O-acetylneuraminate + H2O = N-acetylneuraminate + acetate + H⁺

N-acetyl-9-O-acetylneuraminate + H2O = N-acetylneuraminate + acetate + H(+) (Bound ligand (Het Group name = NAG) matches with 59.09% similarity)

N-acetyl-4-O-acetylneuraminate + H2O = N-acetylneuraminate + acetate + H(+) (Bound ligand (Het Group name = NAG) matches with 59.09% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/23974

Nature 396:92-96 (1998)

PubMed id: 9817207

Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus.

P.B.Rosenthal, X.Zhang, F.Formanowski, W.Fitz, C.H.Wong, H.Meier-Ewert, J.J.Skehel, D.C.Wiley.

ABSTRACT

The spike glycoproteins of the lipid-enveloped orthomyxoviruses and paramyxoviruses have three functions: to recognize the receptor on the cell surface, to mediate viral fusion with the cell membrane, and to destroy the receptor. In influenza C virus, a single glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, possesses all three functions. In influenza A and B, the first two activities are mediated by haemagglutinin and the third by a second glycoprotein, neuraminidase. Here we report the crystal structure of the HEF envelope glycoprotein of influenza C virus. We have identified the receptor-binding site and the receptor-destroying enzyme (9-O-acetylesterase) sites, by using receptor analogues. The receptor-binding domain is structurally similar to the sialic acid-binding domain of influenza A haemagglutinin, but binds 9-O-acetylsialic acid. The esterase domain has a structure similar to the esterase from Streptomyces scabies and a brain acetylhydrolase. The receptor domain is inserted into a surface loop of the esterase domain and the esterase domain is inserted into a surface loop of the stem. The stem domain is similar to that of influenza A haemagglutinin, except that the triple-stranded, alpha-helical bundle diverges at both of its ends, and the amino terminus of HEF2, the fusion peptide, is partially exposed. The segregation of HEF's three functions into structurally distinct domains suggests that the entire stem region, including sequences at the amino and carboxy termini of HEF1 which precede the post-translational cleavage site between HEF1 and HEF2, forms an independent fusion domain which is probably derived from an ancestral membrane fusion protein.

Selected figure(s)

Figure 1.
Figure 1 Haemagglutinin-esterase-fusion glycoprotein structure. a, The structure of the HEF trimer. HEF1 (blue), HEF2 (red), receptor analogue and enzyme inhibitor ligands, yellow; N -linked carbohydrate ball-and-stick (purple). HEF1 is linked to HEF2 by a disulfide bond from Cys 6 of HEF1 to Cys 137 of HEF2. b, Monomer surface of HEF (Grasp27) showing 9-O -acetylsialoside receptor binding site (top) and 9-O -acetylesterase site (bottom). Inset, the esterase removes the acetyl group of 9-O -acetylsialic acid (see arrow).

Figure 3.
Figure 3 HEF receptor binding. a, Ligand bound to the receptor-binding site. Potential hydrogen bonds are indicated in green or red for those conserved in HA ligand binding. Four polar contacts are formed with the ligand identically in HEF and HA: two from the hydroxyl group of HEF1 Tyr 127 (Y98 in HA1) to the 8-hydroxyl and 9-amide of the ligands and two from main-chain atoms: the carbonyl oxygen of HEF1 residue 170 (135 in HA1) to the 5-amide of the ligand and the amide of HEF1 172 (137 in HA1) to the carboxylate of the ligand. The acetyl methyl group binds in a nonpolar pocket unique to HEF, formed by Phe 225 and 293, and Pro 271; the acetyl carbonyl oxygen contacts the hydroxyl group of Tyr 224 and the guanidino group of Arg 236. b, Comparison of architecture of the HEF and HA binding sites. The figure was constructed by superimposing the common parts of the ligands in HA and HEF.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 396, 92-96) copyright 1998.

Figures were selected by an automated process.