Biochemical and Computational Studies of the Interaction between a Glucosamine Derivative, NAPA, and the IKK
IKK
NAPA
UPLC-MS
chondrocytes
molecular docking
molecular dynamics
osteoarthritis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
06 02 2021
06 02 2021
Historique:
received:
01
01
2021
revised:
01
02
2021
accepted:
02
02
2021
entrez:
10
2
2021
pubmed:
11
2
2021
medline:
4
9
2021
Statut:
epublish
Résumé
The glucosamine derivative 2-(N-Acetyl)-L-phenylalanylamido-2-deoxy-β-D-glucose (NAPA), was shown to inhibit the kinase activity of IKKα, one of the two catalytic subunits of IKK complex, decreasing the inflammatory status in osteoarthritis chondrocytes. In the present work we have investigated the inhibition mechanism of IKKα by NAPA by combining computational simulations, in vitro assays and Mass Spectrometry (MS) technique. The kinase in vitro assay was conducted using a recombinant IKKα and IKKtide, a 20 amino acid peptide substrate derived from IkBα kinase protein and containing the serine residues Ser32 and Ser36. Phosphorylated peptide production was measured by Ultra Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC-MS), and the atomic interaction between IKKα and NAPA has been studied by molecular docking and Molecular Dynamics (MD) approaches. Here we report that NAPA was able to inhibit the IKKα kinase activity with an IC
Identifiants
pubmed: 33562013
pii: ijms22041643
doi: 10.3390/ijms22041643
pmc: PMC7915277
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
CHUK protein, human
EC 2.7.11.10
I-kappa B Kinase
EC 2.7.11.10
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Osteoarthritis Cartilage. 2015 Jan;23(1):103-13
pubmed: 25219669
Cell Rep. 2016 Nov 15;17(8):1907-1914
pubmed: 27851956
Pharmacol Ther. 2015 Dec;156:59-68
pubmed: 26478442
J Comput Chem. 2009 Dec;30(16):2785-91
pubmed: 19399780
Sci Rep. 2019 Jun 20;9(1):8905
pubmed: 31222033
Nature. 2004 Apr 8;428(6983):660-4
pubmed: 15071597
Arthritis Res Ther. 2009;11(3):224
pubmed: 19519926
EMBO J. 2002 Oct 15;21(20):5375-85
pubmed: 12374738
J Cheminform. 2015 May 15;7:18
pubmed: 26082804
EMBO Rep. 2014 Jan;15(1):46-61
pubmed: 24375677
J Chem Inf Model. 2011 Oct 24;51(10):2778-86
pubmed: 21919503
Genes Dev. 2012 Feb 1;26(3):203-34
pubmed: 22302935
PLoS Biol. 2013;11(6):e1001581
pubmed: 23776406
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Clin Exp Rheumatol. 2007 Nov-Dec;25(6):847-52
pubmed: 18173918
J Comput Chem. 2010 Mar;31(4):671-90
pubmed: 19575467
Arthritis Res Ther. 2010;12(1):R18
pubmed: 20113495
J Biomol Struct Dyn. 2020 Jun 22;:1-8
pubmed: 32567501
J Biol Chem. 2013 Aug 2;288(31):22758-67
pubmed: 23792959
Rheumatol Int. 2008 Mar;28(5):437-43
pubmed: 17924112
J Biomed Sci. 2013 Jan 23;20:3
pubmed: 23343355
RMD Open. 2015 Aug 15;1(Suppl 1):e000061
pubmed: 26557379
Int J Mol Sci. 2020 Mar 24;21(6):
pubmed: 32213871
Genes Dev. 1999 May 15;13(10):1322-8
pubmed: 10346820
Nat Protoc. 2015 May;10(5):733-55
pubmed: 25855957
Nature. 2011 Apr 21;472(7343):325-30
pubmed: 21423167
Osteoarthritis Cartilage. 2017 Apr;25(4):589-599
pubmed: 27836674
J Chem Inf Model. 2012 Dec 21;52(12):3144-54
pubmed: 23146088
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
J Biol Chem. 2002 Apr 19;277(16):13840-7
pubmed: 11839743
Oncogene. 2006 Oct 30;25(51):6685-705
pubmed: 17072322
Genes Dev. 2004 Sep 15;18(18):2195-224
pubmed: 15371334
Prog Biophys Mol Biol. 2014 Nov-Dec;116(2-3):174-86
pubmed: 24923864
Arthritis Res Ther. 2007;9(5):R104
pubmed: 17925024
J Cheminform. 2012 Aug 13;4(1):17
pubmed: 22889332
J Med Chem. 2015 Dec 10;58(23):9063-88
pubmed: 26230724
Annu Rev Immunol. 2000;18:621-63
pubmed: 10837071
J Comput Chem. 2012 Dec 5;33(31):2451-68
pubmed: 22821581
J Biol Chem. 2001 Sep 28;276(39):36320-6
pubmed: 11470787
Sci Rep. 2019 Sep 19;9(1):13603
pubmed: 31537813
J Biol Chem. 2000 Sep 22;275(38):29779-87
pubmed: 10893415
J Chem Phys. 2007 Jan 7;126(1):014101
pubmed: 17212484
J Chem Inf Model. 2012 Dec 21;52(12):3155-68
pubmed: 23145473
J Biol Chem. 2000 Aug 25;275(34):25883-91
pubmed: 10823818
Cell. 2008 Feb 8;132(3):344-62
pubmed: 18267068