Inhibition of Listeria Monocytogenes HtrA Protease with Camostat, Gabexate and Nafamostat Mesylates and the Binding Mode of the Inhibitors.
High Temperature requirement A (HtrA)
HtrA inhibitors
L. monocytogenes HtrA
Protease activity
Serine protease
Journal
The protein journal
ISSN: 1875-8355
Titre abrégé: Protein J
Pays: Netherlands
ID NLM: 101212092
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
accepted:
12
04
2023
medline:
19
7
2023
pubmed:
24
4
2023
entrez:
24
04
2023
Statut:
ppublish
Résumé
In many bacteria, the High Temperature requirement A (HtrA) protein functions as a chaperone and protease. HtrA is an important factor in stress tolerance and plays a significant role in the virulence of several pathogenic bacteria. Camostat, gabexate and nafamostat mesylates are serine protease inhibitors and have recently shown a great impact in the inhibition studies of SARS-CoV2. In this study, the inhibition of Listeria monocytogenes HtrA (LmHtrA) protease activity was analysed using these three inhibitors. The cleavage assay, using human fibrinogen and casein as substrates, revealed that the three inhibitors effectively inhibit the protease activity of LmHtrA. The agar plate assay and spectrophotometric analysis concluded that the inhibition of nafamostat (IC
Identifiants
pubmed: 37093417
doi: 10.1007/s10930-023-10114-8
pii: 10.1007/s10930-023-10114-8
pmc: PMC10123570
doi:
Substances chimiques
nafamostat
Y25LQ0H97D
Gabexate
4V7M9137X9
camostat
0FD207WKDU
Peptide Hydrolases
EC 3.4.-
RNA, Viral
0
Mesylates
0
Protease Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
343-354Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Dong YK, Kyeong KK (2005) Structure and function of HtrA family proteins, the key players in protein quality control. J Biochem Mol Biol 38:266–274. https://doi.org/10.5483/bmbrep.2005.38.3.266
doi: 10.5483/bmbrep.2005.38.3.266
Hansen G, Hilgenfeld R (2013) Architecture and regulation of HtrA-family proteins involved in protein quality control and stress response. Cell Mol Life Sci 70:761–775. https://doi.org/10.1007/s00018-012-1076-4
doi: 10.1007/s00018-012-1076-4
pubmed: 22806565
Abfalter CM, Bernegger S, Jarzab M et al (2019) The proteolytic activity of Listeria monocytogenes HtrA. BMC Microbiol 19:1–9. https://doi.org/10.1186/s12866-019-1633-1
doi: 10.1186/s12866-019-1633-1
Boehm M, Hoy B, Rohde M et al (2012) Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin. Gut Pathog 4:1–12. https://doi.org/10.1186/1757-4749-4-3
doi: 10.1186/1757-4749-4-3
Hoy B, Löwer M, Weydig C et al (2010) Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion. EMBO Rep 11:798–804. https://doi.org/10.1038/embor.2010.114
doi: 10.1038/embor.2010.114
pubmed: 20814423
pmcid: 2948180
Rigoulay C, Entenza JM, Halpern D et al (2005) Comparative analysis of the roles of HtrA-like surface proteases in two virulent Staphylococcus aureus strains. Infect Immun 73:563–572. https://doi.org/10.1128/IAI.73.1.563-572.2005
doi: 10.1128/IAI.73.1.563-572.2005
pubmed: 15618196
pmcid: 538960
Ibrahim YM, Kerr AR, McCluskey J, Mitchell TJ (2004) Role of HtrA in the virulence and competence of Streptococcus pneumoniae. Infect Immun 72:3584–3591. https://doi.org/10.1128/IAI.72.6.3584-3591.2004
doi: 10.1128/IAI.72.6.3584-3591.2004
pubmed: 15155668
pmcid: 415679
MohamedMohaideen NN, Palaninathan SK, Morin PM et al (2008) Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis. Biochemistry 47:6092–6102. https://doi.org/10.1021/bi701929m
doi: 10.1021/bi701929m
pubmed: 18479146
Xue RY, Liu C, Xiao QT et al (2021) HtrA family proteases of bacterial pathogens: pros and cons for their therapeutic use. Clin Microbiol Infect 27:559–564. https://doi.org/10.1016/j.cmi.2020.12.017
doi: 10.1016/j.cmi.2020.12.017
pubmed: 33359376
Radhakrishnan D, Amrutha MC, Hutterer E et al (2021) High temperature requirement A (HtrA) protease of Listeria monocytogenes and its interaction with extracellular matrix molecules. FEMS Microbiol Lett 368:1–11. https://doi.org/10.1093/femsle/fnab141
doi: 10.1093/femsle/fnab141
Shrimp JH, Kales SC, Sanderson PE et al (2020) An enzymatic TMPRSS2 assay for Assessment of clinical candidates and Discovery of inhibitors as potential treatment of COVID-19. ACS Pharmacol Transl Sci 3:997–1007. https://doi.org/10.1021/acsptsci.0c00106
doi: 10.1021/acsptsci.0c00106
pubmed: 33062952
pmcid: 7507803
Sun G, Sui Y, Zhou Y et al (2021) Structural basis of covalent inhibitory mechanism of TMPRSS2-Related serine proteases by Camostat. J Virol 95:e0086121. https://doi.org/10.1128/jvi.00861-21
doi: 10.1128/jvi.00861-21
pubmed: 34160253
Mahoney M, Damalanka VC, Tartell MA et al (2021) A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. Proc Natl Acad Sci U S A 118:e2108728118. https://doi.org/10.1073/pnas.2108728118
doi: 10.1073/pnas.2108728118
pubmed: 34635581
pmcid: 8694051
Nimishakavi S, Raymond WW, Gruenert DC, Caughey GH (2015) Divergent inhibitor susceptibility among airway lumen-accessible tryptic proteases. PLoS ONE 10:1–17. https://doi.org/10.1371/journal.pone.0141169
doi: 10.1371/journal.pone.0141169
Zhou Y, Vedantham P, Lu K et al (2015) Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res 116:76–84. https://doi.org/10.1016/j.antiviral.2015.01.011
doi: 10.1016/j.antiviral.2015.01.011
pubmed: 25666761
pmcid: 4774534
Yamaya M, Shimotai Y, Hatachi Y et al (2015) The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther 33:66–74. https://doi.org/10.1016/j.pupt.2015.07.001
doi: 10.1016/j.pupt.2015.07.001
pubmed: 26166259
pmcid: 7110702
Sun W, Zhang X, Cummings MD et al (2020) Targeting enteropeptidase with reversible covalent inhibitors to achieve metabolic benefits. J Pharmacol Exp Ther 375:510–521. https://doi.org/10.1124/JPET.120.000219
doi: 10.1124/JPET.120.000219
pubmed: 33033171
Homma S, Hayashi K, Yoshida K et al (2018) Nafamostat mesilate, a serine protease inhibitor, suppresses interferon-gamma-induced up-regulation of programmed cell death ligand 1 in human cancer cells. Int Immunopharmacol 54:39–45. https://doi.org/10.1016/j.intimp.2017.10.016
doi: 10.1016/j.intimp.2017.10.016
pubmed: 29100036
Yan Y, Yang J, Xiao D et al (2022) Nafamostat mesylate as a broad-spectrum candidate for the treatment of flavivirus infections by targeting envelope proteins. Antiviral Res 202:105325. https://doi.org/10.1016/j.antiviral.2022.105325
doi: 10.1016/j.antiviral.2022.105325
pubmed: 35460703
Mori S, Itoh Y, Shinohata R et al (2003) Nafamostat mesilate is an extremely potent inhibitor of human tryptase. J Pharmacol Sci 92:420–423. https://doi.org/10.1254/jphs.92.420
doi: 10.1254/jphs.92.420
pubmed: 12939527
Hoffmann M, Schroeder S, Kleine-Weber H et al (2020) Nafamostat mesylate blocks activation of SARS-CoV-2: new treatment option for COVID-19. Antimicrob Agents Chemother 64:1–7. https://doi.org/10.1128/AAC.00754-20
doi: 10.1128/AAC.00754-20
Jang S, Rhee JY (2020) Three cases of treatment with nafamostat in elderly patients with COVID-19 pneumonia who need oxygen therapy. Int J Infect Dis 96:500–502. https://doi.org/10.1016/j.ijid.2020.05.072
doi: 10.1016/j.ijid.2020.05.072
pubmed: 32470602
pmcid: 7250091
Han SJ, Han W, Song HJ et al (2018) Validation of nafamostat mesilate as an anticoagulant in extracorporeal membrane oxygenation: a large-animal experiment. Korean J Thorac Cardiovasc Surg 51:114–121. https://doi.org/10.5090/kjtcs.2018.51.2.114
doi: 10.5090/kjtcs.2018.51.2.114
pubmed: 29662809
pmcid: 5894575
Yoon WH, Jung YJ, Kim TD et al (2004) Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by reducing matrix metalloproteinases and angiogenesis. Clin Cancer Res 10:4517–4526. https://doi.org/10.1158/1078-0432.CCR-04-0084
doi: 10.1158/1078-0432.CCR-04-0084
pubmed: 15240544
Yuksel M, Okajima K, Uchiba M, Okabe H (2003) Gabexate mesilate, a synthetic protease inhibitor, inhibits lipopolysaccharide-induced tumor necrosis factor-α production by inhibiting activation of both nuclear factor-κB and activator protein-1 in human monocytes. J Pharmacol Exp Ther 305:298–305. https://doi.org/10.1124/jpet.102.041988
doi: 10.1124/jpet.102.041988
pubmed: 12649382
Jae HC, In SL, Hyung KK et al (2009) Nafamostat for prophylaxis against post-endoscopic retrograde cholangiopancreatography pancreatitis compared with gabexate. Gut Liver 3:205–210. https://doi.org/10.5009/gnl.2009.3.3.205
doi: 10.5009/gnl.2009.3.3.205
Dallakyan S, Olson A (2015) Small- molecule Library Screening by docking with PyRx. Methods Mol Biol 1263:243–250. https://doi.org/10.1007/978-1-4939-2269-7
doi: 10.1007/978-1-4939-2269-7
pubmed: 25618350
Spraggon G, Hornsby M, Shipway A et al (2009) Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations. Protein Sci 18:1081–1094. https://doi.org/10.1002/pro.118
doi: 10.1002/pro.118
pubmed: 19388054
pmcid: 2771310
Ponnuraj K, Xu Y, MacOn K et al (2004) Structural analysis of engineered bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. Mol Cell 14:17–28. https://doi.org/10.1016/S1097-2765(04)00160-1
doi: 10.1016/S1097-2765(04)00160-1
pubmed: 15068800
Zhou Y, Wu J, Xue G et al (2022) Structural study of the uPA-nafamostat complex reveals a covalent inhibitory mechanism of nafamostat. Biophys J 18:3940–3949. https://doi.org/10.1016/j.bpj.2022.08.034
doi: 10.1016/j.bpj.2022.08.034
Fraser BJ, Beldar S, Seitova A et al (2022) Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation. Nat Chem Biol 18:963–971. https://doi.org/10.1038/s41589-022-01059-7
doi: 10.1038/s41589-022-01059-7
pubmed: 35676539
Wessler S, Schneider G, Backert S (2017) Bacterial serine protease HtrA as a promising new target for antimicrobial therapy? Cell Commun Signal 15:1–5. https://doi.org/10.1186/s12964-017-0162-533
doi: 10.1186/s12964-017-0162-533
Hauske P, Meltzer M, Ottmann C et al (2009) Selectivity profiling of DegP substrates and inhibitors. Bioorg Med Chem 17:2920–2924. https://doi.org/10.1016/j.bmc.2009.01.073
doi: 10.1016/j.bmc.2009.01.073
pubmed: 19233659
Perna AM, Rodrigues T, Schmidt TP et al (2015) Fragment-based De Novo Design reveals a small-molecule inhibitor of Helicobacter Pylori HtrA. Angew Chem Int Ed Engl 54:10244–10248. https://doi.org/10.1002/anie.201504035
doi: 10.1002/anie.201504035
pubmed: 26069090
pmcid: 6311382
Gloeckl S, Ong VA, Patel P et al (2013) Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis. Mol Microbiol 89:676–689. https://doi.org/10.1111/mmi.12306
doi: 10.1111/mmi.12306
pubmed: 23796320
Agbowuro AA, Hwang J, Peel E et al (2019) Structure-activity analysis of peptidic Chlamydia HtrA inhibitors. Bioorg Med Chem 27:4185–4199. https://doi.org/10.1016/j.bmc.2019.07.049
doi: 10.1016/j.bmc.2019.07.049
pubmed: 31395511
Hwang J, Strange N, Phillips MJA et al (2021) Optimization of peptide-based inhibitors targeting the HtrA serine protease in Chlamydia: design, synthesis and biological evaluation of pyridone-based and N-Capping group-modified analogues. Eur J Med Chem 224:113692. https://doi.org/10.1016/j.ejmech.2021.113692
doi: 10.1016/j.ejmech.2021.113692
pubmed: 34265463
Hwang J, Strange N, Mazraani R et al (2022) Design, synthesis and biological evaluation of P2-modified proline analogues targeting the HtrA serine protease in Chlamydia. Eur J Med Chem 230:114064. https://doi.org/10.1016/j.ejmech.2021.114064
doi: 10.1016/j.ejmech.2021.114064
pubmed: 35007862
Zhu H, Du W, Song M et al (2021) Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2. Comput Struct Biotechnol J 19:467–476. https://doi.org/10.1016/j.csbj.2020.12.035
doi: 10.1016/j.csbj.2020.12.035
pubmed: 33505639
Bernegger S, Brunner C, Vizovišek M et al (2020) A novel FRET peptide assay reveals efficient Helicobacter pylori HtrA inhibition through zinc and copper binding. Sci Rep 10:1–13. https://doi.org/10.1038/s41598-020-67578-2
doi: 10.1038/s41598-020-67578-2