PDBsum entry 6t4c

Virus

PDB id: 6t4c

Contents

Protein chains

271 a.a.

244 a.a.

243 a.a.

48 a.a.

Ligands

STE

SO4 ×6

GOL ×2

GSH

Metals

__K ×4

Waters ×717

PDB id:

6t4c

Name:

Virus

Title:

Bovine enterovirus f3 in complex with glutathione

Structure:

Vp1. Chain: a. Ec: 3.4.22.29,3.6.1.15,3.4.22.28,2.7.7.48. Vp2. Chain: b. Ec: 3.4.22.29,3.6.1.15,3.4.22.28,2.7.7.48. Vp3. Chain: c. Ec: 3.4.22.29,3.6.1.15,3.4.22.28,2.7.7.48.

Source:

Enterovirus f. Organism_taxid: 1330520. Organism_taxid: 1330520

Resolution:

1.80Å R-factor: 0.205 R-free: 0.208

Authors:

H.M.E.Duyvesteyn,J.Ren,T.S.Walter,E.E.Fry,D.I.Stuart

Key ref:

H.M.E.Duyvesteyn et al. (2020). Glutathione facilitates enterovirus assembly by binding at a druggable pocket. Commun Biol, 3, 9. PubMed id: 31909201 DOI: 10.1038/s42003-019-0722-x

Date:

13-Oct-19 Release date: 15-Jan-20

Protein chain

Q2LKZ0  (Q2LKZ0_9ENTO) -  Genome polyprotein from Enterovirus F

Seq: 2166 a.a.

Struc: 271 a.a.

Protein chain

Q2LKZ0  (Q2LKZ0_9ENTO) -  Genome polyprotein from Enterovirus F

Seq: 2166 a.a.

Struc: 244 a.a.

Protein chain

Q2LKZ0  (Q2LKZ0_9ENTO) -  Genome polyprotein from Enterovirus F

Seq: 2166 a.a.

Struc: 243 a.a.*

Protein chain

Q2LKZ0  (Q2LKZ0_9ENTO) -  Genome polyprotein from Enterovirus F

Seq: 2166 a.a.

Struc: 48 a.a.

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 3: Chains A, B, C, D: E.C.3.4.22.28 - picornain 3C.
• Reaction: Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 4: Chains A, B, C, D: E.C.3.4.22.29 - picornain 2A.
• Reaction: Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.
• Enzyme class 5: Chains A, B, C, D: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1038/s42003-019-0722-x

Commun Biol 3:9 (2020)

PubMed id: 31909201

Glutathione facilitates enterovirus assembly by binding at a druggable pocket.

H.M.E.Duyvesteyn, J.Ren, T.S.Walter, E.E.Fry, D.I.Stuart.

ABSTRACT

Enteroviruses cause a range of human and animal diseases, some life-threatening, but there remain no licenced anti-enterovirus drugs. However, a benzene-sulfonamide derivative and related compounds have been shown recently to block infection of a range of enteroviruses by binding the capsid at a positively-charged surface depression conserved across many enteroviruses. It has also been established that glutathione is essential for the assembly of many enteroviruses, interacting with the capsid proteins to facilitate the formation of the pentameric assembly intermediate, although the mechanism is unknown. Here we show, by high resolution structure analyses of enterovirus F3, that reduced glutathione binds to the same interprotomer pocket as the benzene-sulfonamide derivative. Bound glutathione makes strong interactions with adjacent protomers, thereby explaining the underlying biological role of this druggable binding pocket and delineating the pharmacophore for potential antivirals.