Show simple item record

dc.contributor.authorHassani, Sorour
dc.contributor.authorGharechaei, Behzad
dc.contributor.authorNikfard, Somayeh
dc.contributor.authorFazli, Mostafa
dc.contributor.authorGheibi, Nematollah
dc.contributor.authorHardre, Renaud
dc.contributor.authorLegge, Raymond L.
dc.contributor.authorHaghbeen, Kamahldin
dc.date.accessioned2018-10-18 16:13:15 (GMT)
dc.date.available2018-10-18 16:13:15 (GMT)
dc.date.issued2018-07-01
dc.identifier.urihttps://dx.doi.org/10.1016/j.ijbiomac.2018.03.185
dc.identifier.urihttp://hdl.handle.net/10012/14016
dc.descriptionThe final publication is available at Elsevier via https://dx.doi.org/10.1016/j.ijbiomac.2018.03.185 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.description.abstractKinetics studies of L-tyrosine (LTy) ortho-hydroxylation by mushroom tyrosinase (MT) confirmed that MT was severely, but not completely, inhibited at higher concentrations of LTy. Despite the availability of the crystal structure reports, no allosteric site has been identified on MT. To examine the assumption that a non-specific binding site works as a regulatory site, docking simulations were run for the second molecule of L-tyrosine (LTy(2)) on the complexes of the first L-tyrosine molecule (LTy(1)) with the heavy chain (H) of MT (LTy(1)/HMT) and its dimer with the light chain (Ty(1)/LHMT). In both, LTy(2) occupied a non-specific binding site (MTPc). MD simulations revealed LTy(2)/HMT/LTy(1) and LTy(2)/LHMT/LTy(1) were stable. Binding free-energy analysis supported the formation of LTy(2)/HMT/LTy(1) and LTy(2)/LHMT/LTy(1) at higher concentrations of LTy and disclosed the importance of Delta E-elec and Delta G(polar) during binding of LTy(2) to MTPc. Upon LTy(2) binding to MTPc, the Cu-Cu distance remained unchanged while the spatial position of LTy(1) in the active site (MTPa) changed so that it would not be able to participate in ortho-hydroxylation. This study suggests a tuning role for L chain during binding of the ligands to MTPa and MTPc. Given these results, a plausible mechanism was proposed for the MT substrate inhibition.en
dc.description.sponsorshipIran National Science Foundation [93031596]en
dc.language.isoenen
dc.publisherElsevieren
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectSubstrate inhibitionen
dc.subjectRegulatory siteen
dc.subjectNon-specific binding siteen
dc.titleNew insight into the allosteric effect of L-tyrosine on mushroom tyrosinase during L-dopa productionen
dc.typeArticleen
dcterms.bibliographicCitationHassani, S., Gharechaei, B., Nikfard, S., Fazli, M., Gheibi, N., Hardré, R., … Haghbeen, K. (2018). New insight into the allosteric effect of L-tyrosine on mushroom tyrosinase during L-dopa production. International Journal of Biological Macromolecules, 114, 821–829. doi:10.1016/j.ijbiomac.2018.03.185en
uws.contributor.affiliation1Faculty of Engineeringen
uws.contributor.affiliation2Chemical Engineeringen
uws.typeOfResourceTexten
uws.typeOfResourceTexten
uws.peerReviewStatusRevieweden
uws.scholarLevelFacultyen


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International

UWSpace

University of Waterloo Library
200 University Avenue West
Waterloo, Ontario, Canada N2L 3G1
519 888 4883

All items in UWSpace are protected by copyright, with all rights reserved.

DSpace software

Service outages