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dc.contributor.authorImai, Kyohei
dc.contributor.authorSaito, Rysouke
dc.contributor.authorEzawa, Takyua
dc.contributor.authorSugiyama, Satoshi
dc.contributor.authorSylte, Ingebrigt
dc.contributor.authorKurita, Noriyuki
dc.date.accessioned2023-03-13T11:50:41Z
dc.date.available2023-03-13T11:50:41Z
dc.date.issued2022-10-11
dc.description.abstractThe zinc metalloprotease pseudolysin (PLN) secreted from Pseudomonas aeruginosa degrades extracellular proteins to produce bacterial nutrition, and various types of PLN inhibitors have been developed to suppress the bacterial growth. However, as the structure of the ligand-binding pocket of PLN has large similarities to those of human matrix metalloproteinases (MMPs) and other human zinc metalloprotease, there is a risk that PLN inhibitors also inhibit human zinc proteases. In this study, we propose a novel agent that may bind stronger to PLN than to MMPs. The compound is proposed based on the specific molecular interactions between existing agents and PLN/MMP metalloproteases evaluated by the present molecular simulations. First, we confirmed that the binding energies of PLN agents evaluated using the ab initio fragment molecular orbital method were comparable to the IC50 values obtained through previous experiments. In addition, the specific molecular interactions between these agents and MMP-9 were investigated to elucidate the fact that some of the agents bind weaker to MMP than PLN. Based on the results, we proposed a novel agent having a succinimide group introduce by a hydroxamic acid group and investigated its binding properties with PLN and MMP. The results may provide useful information for the development of potent inhibitors for PLN with few potential side effects in human bodies.en_US
dc.identifier.citationImai, Saito, Ezawa, Sugiyama, Sylte, Kurita. Proposal of selective inhibitor for bacterial zinc metalloprotease: Molecular mechanics and ab initio molecular orbital calculations. Journal of Molecular Graphics and Modelling. 2022;110en_US
dc.identifier.cristinIDFRIDAID 2001142
dc.identifier.doi10.1016/j.jmgm.2021.108047
dc.identifier.issn1093-3263
dc.identifier.issn1873-4243
dc.identifier.urihttps://hdl.handle.net/10037/28719
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalJournal of Molecular Graphics and Modelling
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.subjectVDP::Medisinske fag: 700en_US
dc.subjectVDP::Midical sciences: 700en_US
dc.titleProposal of selective inhibitor for bacterial zinc metalloprotease: Molecular mechanics and ab initio molecular orbital calculationsen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)