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PDBsum entry 5r81
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Hydrolase/hydrolase inhibitor
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PDB id
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5r81
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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Pandda analysis group deposition -- crystal structure of covid-19 main protease in complex with z1367324110
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Structure:
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3c-like proteinase. Chain: a. Synonym: sars-cov-2 main protease,3cl-pro,3clp,main protease,mpro, non-structural protein 5,nsp5,sars coronavirus main proteinase. Engineered: yes
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Source:
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Severe acute respiratory syndrome coronavirus 2. 2019-ncov. Organism_taxid: 2697049. Gene: rep, 1a-1b. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.95Å
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R-factor:
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0.185
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R-free:
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0.249
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Authors:
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D.Fearon,A.J.Powell,A.Douangamath,C.D.Owen,C.Wild,T.Krojer,P.Lukacik, C.M.Strain-Damerell,M.A.Walsh,F.Von Delft
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Key ref:
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A.Douangamath
et al.
(2020).
Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease.
Nat Commun,
11,
5047.
PubMed id:
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Date:
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03-Mar-20
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Release date:
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11-Mar-20
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PROCHECK
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Headers
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References
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Nat Commun
11:5047
(2020)
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PubMed id:
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Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease.
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A.Douangamath,
D.Fearon,
P.Gehrtz,
T.Krojer,
P.Lukacik,
C.D.Owen,
E.Resnick,
C.Strain-Damerell,
A.Aimon,
P.Ábrányi-Balogh,
J.Brandão-Neto,
A.Carbery,
G.Davison,
A.Dias,
T.D.Downes,
L.Dunnett,
M.Fairhead,
J.D.Firth,
S.P.Jones,
A.Keeley,
G.M.Keserü,
H.F.Klein,
M.P.Martin,
M.E.M.Noble,
P.O'Brien,
A.Powell,
R.N.Reddi,
R.Skyner,
M.Snee,
M.J.Waring,
C.Wild,
N.London,
F.von Delft,
M.A.Walsh.
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ABSTRACT
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COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no
antiviral drugs or vaccines were developed against the closely related
coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To
identify starting points for such therapeutics, we performed a large-scale
screen of electrophile and non-covalent fragments through a combined mass
spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two
cysteine viral proteases essential for viral replication. Our crystallographic
screen identified 71 hits that span the entire active site, as well as 3 hits at
the dimer interface. These structures reveal routes to rapidly develop more
potent inhibitors through merging of covalent and non-covalent fragment hits;
one series of low-reactivity, tractable covalent fragments were progressed to
discover improved binders. These combined hits offer unprecedented structural
and reactivity information for on-going structure-based drug design against
SARS-CoV-2 main protease.
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');
}
}
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Links
