PDBsum entry 1qol

Hydrolase

PDB id: 1qol

Contents

Protein chains

(+ 2 more) 166 a.a. *

Ligands

EDO ×3

Metals

_CL ×3

* Residue conservation analysis

PDB id:

1qol

Name:

Hydrolase

Title:

Structure of the fmdv leader protease

Structure:

Protease (nonstructural protein p20a). Chain: a, b, c, d, e, f, g, h. Synonym: leader protease. Engineered: yes. Mutation: yes

Source:

Foot-and-mouth disease virus. Organism_taxid: 73482. Strain: o1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.258 R-free: 0.314

Authors:

A.Guarne,J.Tormo,R.Kirchweger,D.Pfistermueller,T.Skern,I.Fita

Key ref:

A.Guarné et al. (1998). Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition. Embo J, 17, 7469-7479. PubMed id: 9857201

Date:

13-Nov-99 Release date: 10-Nov-00

Protein chains

P03305  (POLG_FMDVO) -  Genome polyprotein from Foot-and-mouth disease virus serotype O

Seq: 2332 a.a.

Struc: 166 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 2: 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 3: E.C.3.4.22.46 - L-peptidase.
• Reaction: Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a Lys-|-Gly bond, but then cleaves host cell initiation factor eIF-4G at bonds -Gly-|-Arg- and -Lys-|-Arg-.
• Enzyme class 4: 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

Embo J 17:7469-7479 (1998)

PubMed id: 9857201

Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition.

A.Guarné, J.Tormo, R.Kirchweger, D.Pfistermueller, I.Fita, T.Skern.

ABSTRACT

The leader protease of foot-and-mouth disease virus, as well as cleaving itself from the nascent viral polyprotein, disables host cell protein synthesis by specific proteolysis of a cellular protein: the eukaryotic initiation factor 4G (eIF4G). The crystal structure of the leader protease presented here comprises a globular catalytic domain reminiscent of that of cysteine proteases of the papain superfamily, and a flexible C-terminal extension found intruding into the substrate-binding site of an adjacent molecule. Nevertheless, the relative disposition of this extension and the globular domain to each other supports intramolecular self-processing. The different sequences of the two substrates cleaved during viral replication, the viral polyprotein (at LysLeuLys/GlyAlaGly) and eIF4G (at AsnLeuGly/ArgThrThr), appear to be recognized by distinct features in a narrow, negatively charged groove traversing the active centre. The structure illustrates how the prototype papain fold has been adapted to the requirements of an RNA virus. Thus, the protein scaffold has been reduced to a minimum core domain, with the active site being modified to increase specificity. Furthermore, surface features have been developed which enable C-terminal self-processing from the viral polyprotein.