An integrated molecular modeling approach for the tryptase monomer–curcuminoid recognition analysis: conformational and bioenergetic features
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Human mast cell tryptase has been shown as an activating enzyme in matrix degradation process. The previous study suggest that tryptase either alone or in joining with activation of metalloproteinases, can associate in extra cellular matrix damage and the possible destruction of the basement membrane resulting in photoaging. Therefore the inhibition of tryptase activity is one of the most important therapeutic strategies against the photoaging. Curcumin has been shown to be a potential agent for preventing and/or treating the photoaging induced by UV radiation. However, the protective effect of curcumin against the photoaging through the tryptase inhibition is still inadequately understood. In this work, computational methods to characterize the structural framework and define the atomistic details of the determinants for the tryptase inhibition mechanism by curcuminoids were performed. By molecular docking, three putative binding models able to efficiently bind all curcuminoids were identified. Analysis of molecular dynamics simulations revealed that cyclocurcumin, curcumin glucuronide, and curcumin, the most effective inhibitors from the three models, modified significant tryptase monomer rigidity by binding in all the possible sites. The result of these binding events is the suppression of the functional enzymatic motions involving the binding of substrates to the catalytic site. On the basis of this finding may thus be beneficial for the development of new natural inhibitors for the therapeutic remedy of photoaging, targeting and modulating the activity of tryptase.
KeywordsAnti-aging Curcuma longa Curcuminoids Molecular docking Molecular dynamics simulation Photoaging Tryptase
The authors would like to thank Inte:Ligand Software-Entwicklungs und Consulting GmbH for providing an academic free license for LigandScout 4.2.1.
Compliance with ethical standards
This article does not contain any study with human or animal subjects performed by any of the authors.
Conflict of interest
Every author declares no conflict of interest.
- Case DA, IYB-S SR, Brozell DS, Cerutti TE, Cheatham VWD III, Cruzeiro TA, Darden RE, Duke D, Ghoreishi MK, Gilson H, Gohlke AW, Goetz D, Greene R, Harris N, Homeyer S, Izadi A, Kovalenko T, Kurtzman TS, Lee S, LeGrand P, Li C, Lin J, Liu T, Luchko R, Luo DJ, Mermelstein KM, Merz Y, Miao G, Monard C, Nguyen H, Nguyen I, Omelyan A, Onufriev F, Pan R, Qi DR, Roe A, Roitberg C, Sagui S, Schott-Verdugo J, Shen CL, Simmerling J, Smith R, Salomon-Ferrer J, Swails RC, Walker J, Wang H, Wei RM, Wolf XW, Xiao L, York DM, Kollman PA (2018) AMBER 2018. University of California, San FranciscoGoogle Scholar
- Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J, Kollman P (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24:1999–2012. https://doi.org/10.1002/jcc.10349 CrossRefPubMedGoogle Scholar
- Iddamalgoda A, Le QT, Ito K, Tanaka K, Kojima H, Kido H (2008) Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins. Arch Dermatol Res 300(Suppl 1):S69–S76. https://doi.org/10.1007/s00403-007-0806-1 CrossRefPubMedPubMedCentralGoogle Scholar
- Jiang QQ, Bartsch L, Sicking W, Wich PR, Heider D, Hoffmann D, Schmuck C (2013) A new approach to inhibit human beta-tryptase by protein surface binding of four-armed peptide ligands with two different sets of arms. Org Biomol Chem 11:1631–1639. https://doi.org/10.1039/c3ob27302d CrossRefPubMedGoogle Scholar
- Liang G, Aldous S, Merriman G, Levell J, Pribish J, Cairns J, Chen X, Maignan S, Mathieu M, Tsay J, Sides K, Rebello S, Whitely B, Morize I, Pauls HW (2012) Structure-based library design and the discovery of a potent and selective mast cell beta-tryptase inhibitor as an oral therapeutic agent. Bioorg Med Chem Lett 22:1049–1054. https://doi.org/10.1016/j.bmcl.2011.11.119 CrossRefPubMedGoogle Scholar
- Punkvang A, Hannongbua S, Saparpakorn P, Pungpo P (2016) Insight into the structural requirements of aminopyrimidine derivatives for good potency against both purified enzyme and whole cells of M. tuberculosis: combination of HQSAR, CoMSIA, and MD simulation studies. J Biomol Struct Dyn 34:1079–1091. https://doi.org/10.1080/07391102.2015.1068711 CrossRefPubMedGoogle Scholar
- Rout AK, Dehury B, Maharana J, Nayak C, Baisvar VS, Behera BK, Das BK (2018) Deep insights into the mode of ATP-binding mechanism in zebrafish cyclin-dependent protein kinase-like 1 (zCDKL1): a molecular dynamics approach. J Mol Graph Model 81:175–183. https://doi.org/10.1016/j.jmgm.2018.02.002 CrossRefPubMedGoogle Scholar