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Design of galardine analogs as putative psudolysin inhibitors based on ab initio fragment molecular orbital calculations.
Ezawa, Takuya; Sugiyama, Satoshi; Ara, Ayami; Sylte, Ingebrigt; Kurita, Noriyuki.
Afiliação
  • Ezawa T; Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Japan.
  • Sugiyama S; Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Japan.
  • Ara A; Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Japan.
  • Sylte I; Department of Medical Biology, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromso, Norway.
  • Kurita N; Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Japan.
J Biomol Struct Dyn ; 38(11): 3307-3317, 2020 Jul.
Article em En | MEDLINE | ID: mdl-31422741
Pseudolysin (PLN) is a metalloproteinase secreted from bacteria that degrades extracellular proteins to produce bacterial nutrition. It is thus expected that inhibitors against PLN can suppress the growth of bacteria and their pandemic spread. In addition, since these inhibitors do not attack to bacteria directly, there is a reduced risk for producing drug-resistant bacteria. On the other hand, as PLN has large structural similarity in the active sites with human matrix-metalloproteinases (MMPs), there is a possibility that the inhibitors for PLN also inhibit MMP activity, resulting in a loss of necessary nutrients to be produced by MMPs. Therefore, it is required the agents inhibiting the activity of only PLN not MMPs. In the present study, we employed a hydroxamate compound galardin, which has a significant inhibition effect against PLN and MMP, and investigated its specific interactions with PLN/MMP at atomic and electronic levels, by use of ab initio molecular simulations. Based on the results, we proposed several derivatives of galardin and elucidated which derivatives that can bind more strongly to PLN and be putative antimicrobial agents capable of inhibiting the PLN activity.Communicated by Ramaswamy H. Sarma.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metaloproteinases da Matriz / Inibidores de Metaloproteinases de Matriz Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Metaloproteinases da Matriz / Inibidores de Metaloproteinases de Matriz Idioma: En Ano de publicação: 2020 Tipo de documento: Article