PDBsum entry 2j92

Hydrolase

PDB id: 2j92

Contents

Protein chains

201 a.a. *

185 a.a. *

Waters ×109

* Residue conservation analysis

PDB id:

2j92

Name:

Hydrolase

Title:

3c protease from type a10(61) foot-and-mouth disease virus - crystal packing mutant (k51q)

Structure:

Picornain 3c. Chain: a, b. Synonym: protease 3c, p3c, protease p20b, 3c protease. Engineered: yes. Mutation: yes. Other_details: k51q - to disrupt original crystal packing c95k - to avoid aggregation c142s - to avoid aggregation c163a - to remove acitve-ste nucleophile.

Source:

Foot-and-mouth disease virus (strain a10-61). Organism_taxid: 12112. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.229 R-free: 0.254

Authors:

T.R.Sweeney,J.R.Birtley,R.J.Leatherbarrow,S.Curry

Key ref:

T.R.Sweeney et al. (2007). Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis. J Virol, 81, 115-124. PubMed id: 17065215

Date:

01-Nov-06 Release date: 21-Dec-06

Protein chain

P03306  (POLG_FMDV1) -  Genome polyprotein from Foot-and-mouth disease virus (strain A10-61)

Seq: 2332 a.a.

Struc: 201 a.a.*

Protein chain

P03306  (POLG_FMDV1) -  Genome polyprotein from Foot-and-mouth disease virus (strain A10-61)

Seq: 2332 a.a.

Struc: 185 a.a.*

* PDB and UniProt seqs differ at 12 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, B: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 2: Chains A, B: 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: Chains A, B: 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: Chains A, B: 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

J Virol 81:115-124 (2007)

PubMed id: 17065215

Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis.

T.R.Sweeney, N.Roqué-Rosell, J.R.Birtley, R.J.Leatherbarrow, S.Curry.

ABSTRACT

The 3C protease (3C(pro)) from foot-and-mouth disease virus (FMDV), the causative agent of a widespread and economically devastating disease of domestic livestock, is a potential target for antiviral drug design. We have determined the structure of a new crystal form of FMDV 3C(pro), a chymotrypsin-like cysteine protease, which reveals features that are important for catalytic activity. In particular, we show that a surface loop which was disordered in previous structures adopts a beta-ribbon structure that is conformationally similar to equivalent regions on other picornaviral 3C proteases and some serine proteases. This beta-ribbon folds over the peptide binding cleft and clearly contributes to substrate recognition. Replacement of Cys142 at the tip of the beta-ribbon with different amino acids has a significant impact on enzyme activity and shows that higher activity is obtained with more hydrophobic side chains. Comparison of the structure of FMDV 3C(pro) with homologous enzyme-peptide complexes suggests that this correlation arises because the side chain of Cys142 contacts the hydrophobic portions of the P2 and P4 residues in the peptide substrate. Collectively, these findings provide compelling evidence for the role of the beta-ribbon in catalytic activity and provide valuable insights for the design of FMDV 3C(pro) inhibitors.