PDBsum entry 2v6n

Viral protein

PDB id: 2v6n

Contents

Protein chain

306 a.a. *

Ligands

XP1

MES

SO4

Waters ×361

* Residue conservation analysis

PDB id:

2v6n

Name:

Viral protein

Title:

Crystal structures of the sars-coronavirus main proteinase inactivated by benzotriazole compounds

Structure:

Replicase polyprotein 1ab. Chain: a. Fragment: sars-cov main proteinase, residues 3241-3546. Synonym: pp1ab, orf1ab polyprotein. Engineered: yes

Source:

Human sars coronavirus. Sars-cov. Organism_taxid: 227859. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.98Å R-factor: 0.166 R-free: 0.211

Authors:

K.H.G.Verschueren,K.Pumpor,S.Anemueller,J.R.Mesters,R.Hilgenfeld

Key ref:

K.H.Verschueren et al. (2008). A structural view of the inactivation of the SARS coronavirus main proteinase by benzotriazole esters. Chem Biol, 15, 597-606. PubMed id: 18559270

Date:

19-Jul-07 Release date: 01-Jul-08

Protein chain

P0C6X7  (R1AB_CVHSA) -  Replicase polyprotein 1ab from Severe acute respiratory syndrome coronavirus

Seq: 7073 a.a.

Struc: 306 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.1.1.- - ?????
• Enzyme class 3: E.C.2.1.1.56 - mRNA (guanine-N(7))-methyltransferase.
• Reaction: a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine
• Enzyme class 4: E.C.2.1.1.57 - methyltransferase cap1.
• Reaction: a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H⁺
• Enzyme class 5: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 6: E.C.2.7.7.50 - mRNA guanylyltransferase.
• Reaction: a 5'-end diphospho-ribonucleoside in mRNA + GTP + H⁺ = a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + diphosphate
• Enzyme class 7: E.C.3.1.13.- - ?????
• Enzyme class 8: E.C.3.4.19.12 - ubiquitinyl hydrolase 1.
• Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
• Enzyme class 9: E.C.3.4.22.- - ?????
• Enzyme class 10: E.C.3.4.22.69 - Sars coronavirus main proteinase.
• Enzyme class 11: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺
• Enzyme class 12: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺
• Enzyme class 13: E.C.4.6.1.- - ?????

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

Chem Biol 15:597-606 (2008)

PubMed id: 18559270

A structural view of the inactivation of the SARS coronavirus main proteinase by benzotriazole esters.

K.H.Verschueren, K.Pumpor, S.Anemüller, S.Chen, J.R.Mesters, R.Hilgenfeld.

ABSTRACT

The main proteinase (M(pro)) of the severe acute respiratory syndrome (SARS) coronavirus is a principal target for the design of anticoronaviral compounds. Benzotriazole esters have been reported as potent nonpeptidic inhibitors of the enzyme, but their exact mechanism of action remains unclear. Here we present crystal structures of SARS-CoV M(pro), the active-site cysteine of which has been acylated by benzotriazole esters that act as suicide inhibitors. In one of the structures, the thioester product has been hydrolyzed and benzoic acid is observed to bind to the hydrophobic S2 pocket. This structure also features the enzyme with a shortened N-terminal segment ("amputated N finger"). The results further the understanding of the important role of the N finger for catalysis as well as the design of benzotriazole inhibitors with improved specificity.