Unmasking the Conformational Stability and Inhibitor Binding to SARS-CoV-2 Main Protease Active Site Mutants and Miniprecursor.
SARS CoV-2 main protease
conformational stability
inhibitor binding
monomer–dimer equilibrium
room-temperature X-ray crystallography
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
30 12 2022
30 12 2022
Historique:
received:
13
09
2022
revised:
28
10
2022
accepted:
28
10
2022
pubmed:
6
11
2022
medline:
7
12
2022
entrez:
5
11
2022
Statut:
ppublish
Résumé
We recently demonstrated that inhibitor binding reorganizes the oxyanion loop of a monomeric catalytic domain of SARS CoV-2 main protease (MPro) from an unwound (E) to a wound (active, E*) conformation, independent of dimerization. Here we assess the effect of the flanking N-terminal residues, to imitate the MPro precursor prior to its autoprocessing, on conformational equilibria rendering stability and inhibitor binding. Thermal denaturation (T
Identifiants
pubmed: 36334779
pii: S0022-2836(22)00496-X
doi: 10.1016/j.jmb.2022.167876
pmc: PMC9628131
mid: NIHMS1847336
pii:
doi:
Substances chimiques
3C-like proteinase, SARS-CoV-2
EC 3.4.22.-
Coronavirus 3C Proteases
EC 3.4.22.28
phenylmethyl N-((1S)-1-((((1S)-1-formyl-2-(2-oxo-3-pyrrolidinyl)ethyl)amino)carbonyl)-3-methylbutyl)carbamate
W9SVW656LQ
Coronavirus Protease Inhibitors
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
167876Subventions
Organisme : Intramural NIH HHS
ID : ZIA DK075166
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Commun Biol. 2022 Sep 16;5(1):976
pubmed: 36114420
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
J Med Chem. 2021 Dec 9;64(23):17366-17383
pubmed: 34705466
PLoS One. 2021 Feb 1;16(2):e0245962
pubmed: 33524017
Nat Rev Microbiol. 2021 Mar;19(3):155-170
pubmed: 33116300
Acta Crystallogr D Biol Crystallogr. 2009 Oct;65(Pt 10):1074-80
pubmed: 19770504
J Biol Chem. 2010 Sep 3;285(36):28134-40
pubmed: 20489209
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9072-7
pubmed: 21576495
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):12997-13002
pubmed: 27799534
J Med Chem. 2022 Feb 24;65(4):2848-2865
pubmed: 33891389
Protein Cell. 2011 Apr;2(4):282-90
pubmed: 21533772
Science. 2020 Apr 24;368(6489):409-412
pubmed: 32198291
Protein Sci. 2020 Apr;29(4):1069-1078
pubmed: 31730249
ACS Comb Sci. 2020 Jun 8;22(6):297-305
pubmed: 32402186
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Virology. 2009 Jun 5;388(2):324-34
pubmed: 19409595
J Med Chem. 2022 Jul 14;65(13):9376-9395
pubmed: 35709506
Biophys J. 2000 Mar;78(3):1606-19
pubmed: 10692345
Protein Cell. 2010 Jan;1(1):59-74
pubmed: 21203998
Science. 2021 Mar 26;371(6536):1374-1378
pubmed: 33602867
J Biol Chem. 2008 May 9;283(19):13459-70
pubmed: 18281688
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
Front Mol Biosci. 2020 Dec 17;7:605236
pubmed: 33392262
J Mol Biol. 2021 Sep 3;433(18):167118
pubmed: 34174328
Protein J. 2020 Jun;39(3):198-216
pubmed: 32447571
J Med Virol. 2020 Jun;92(6):667-674
pubmed: 32167180
Biochem Biophys Res Commun. 2005 Apr 15;329(3):934-40
pubmed: 15752746
Biochemistry. 2004 May 4;43(17):4906-12
pubmed: 15109248
Nat Commun. 2020 Jun 24;11(1):3202
pubmed: 32581217
J Virol. 2008 May;82(9):4620-9
pubmed: 18305031
J Med Chem. 2022 Feb 24;65(4):2926-2939
pubmed: 34313428
Structure. 2021 Aug 5;29(8):823-833.e5
pubmed: 34161756
Respir Res. 2005 Jan 20;6:8
pubmed: 15661082
Science. 2021 Dec 24;374(6575):1586-1593
pubmed: 34726479
Curr Protoc Protein Sci. 2013 Feb;Chapter 20:Unit20.12
pubmed: 23377850
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Nat Commun. 2020 Nov 18;11(1):5877
pubmed: 33208735
Methods Cell Biol. 2008;84:143-79
pubmed: 17964931
Commun Biol. 2022 Mar 1;5(1):160
pubmed: 35233052
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Nat Commun. 2022 Apr 27;13(1):2268
pubmed: 35477935
J Biol Chem. 2005 Sep 2;280(35):31257-66
pubmed: 15788388
J Biol Chem. 2008 Jan 4;283(1):554-564
pubmed: 17977841
Biophys J. 2010 Apr 7;98(7):1327-36
pubmed: 20371333
ACS Med Chem Lett. 2020 Oct 25;11(12):2526-2533
pubmed: 33324471
ChemMedChem. 2021 Mar 18;16(6):942-948
pubmed: 33283984
J Biol Chem. 2020 Dec 11;295(50):17365-17373
pubmed: 33060199
Anal Biochem. 2003 Sep 1;320(1):104-24
pubmed: 12895474
Methods Enzymol. 2015;562:109-33
pubmed: 26412649
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508
FEBS J. 2013 May;280(9):2002-13
pubmed: 23452147