 |
PDBsum entry 1p9s
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Coronavirus main proteinase (3clpro) structure: basis for design of anti-Sars drugs.
|
|
|
Authors
|
|
K.Anand,
J.Ziebuhr,
P.Wadhwani,
J.R.Mesters,
R.Hilgenfeld.
|
|
|
Ref.
|
|
Science, 2003,
300,
1763-1767.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
A novel coronavirus has been identified as the causative agent of severe acute
respiratory syndrome (SARS). The viral main proteinase (Mpro, also called
3CLpro), which controls the activities of the coronavirus replication complex,
is an attractive target for therapy. We determined crystal structures for human
coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine
Mpro, and we
constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The
structures reveal a remarkable degree of conservation of the substrate-binding
sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage
of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus
3Cpro inhibitors may be modified to make them useful for treating SARS.
|
|
|
|
|
|
|
|
Figure 2.
Fig. 2. Dimer of HCoV Mpro. The N-terminal residues of each
chain squeeze between domains II and III of the parent monomer
and domain II of the other monomer. N and C termini are labeled
by cyan and magenta spheres and the letters N and C,
respectively.
|
|
Figure 4.
Fig. 4. Derivatives of the antirhinoviral drug AG7088 should
inhibit coronavirus Mpros. A superimposition (stereo image) of
the substrate-binding regions of TGEV Mpro (marine) in complex
with the hexapeptidyl CMK inhibitor (red) and HRV2 3C^pro
(green) in complex with the inhibitor AG7088 (yellow) is shown.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the AAAs:
Science
(2003,
300,
1763-1767)
copyright 2003.
|
|
|
|
|
|
|
