PDBsum entry 2qiq

Viral protein

PDB id: 2qiq

Contents

Protein chain

301 a.a. *

Ligands

CYV

Waters ×161

* Residue conservation analysis

PDB id:

2qiq

Name:

Viral protein

Title:

Structure-based design and synthesis and biological evaluation of peptidomimetic sars-3clpro inhibitors

Structure:

Replicase polyprotein 1ab. Chain: a. Fragment: 3cl proteinase. Engineered: yes

Source:

Sars coronavirus. Organism_taxid: 227859. Gene: rep. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.90Å R-factor: 0.235 R-free: 0.275

Authors:

V.Grum-Tokars

Key ref:

A.K.Ghosh et al. (2007). Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors. Bioorg Med Chem Lett, 17, 5876-5880. PubMed id: 17855091

Date:

05-Jul-07 Release date: 12-Feb-08

Protein chain

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

Seq: 7073 a.a.

Struc: 301 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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

Bioorg Med Chem Lett 17:5876-5880 (2007)

PubMed id: 17855091

Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors.

A.K.Ghosh, K.Xi, V.Grum-Tokars, X.Xu, K.Ratia, W.Fu, K.V.Houser, S.C.Baker, M.E.Johnson, A.D.Mesecar.

ABSTRACT

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P(4)-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.