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Author Vallet, Sylvain ♦ Guéroult, Marc ♦ Belloy, Nicolas ♦ Dauchez, Manuel ♦ Ricard-Blum, Sylvie
Source Hyper Articles en Ligne (HAL)
Content type Text
Publisher ACS Publications
File Format PDF
Language English
Subject Keyword sdv ♦ info ♦ Life Sciences [q-bio] ♦ Computer Science [cs]/Modeling and Simulation
Abstract Lysyl oxidase (LOX) is a cross-linking enzyme identified 50 years ago, but its 3D structure is still unknown. We have thus built a 3D model of human LOX by homology modeling using the X-ray structure of human lysyl oxidase-like 2 as a template. This model is the first one to recapitulate all known biochemical features of LOX, namely, the coordination of the copper ion and the formation of the lysine tyrosylquinone cofactor and the disulfide bridges. Furthermore, this model is stable during a 1 μs molecular dynamics simulation. The catalytic site is located in a groove surrounded by two loops. The distance between these loops fluctuated during the simulations, which suggests that the groove forms a hinge with a variable opening, which is able to accommodate the various sizes of LOX substrates. This 3D model is a prerequisite to perform docking experiments with LOX substrates and other partners to identify binding sites and to design new LOX inhibitors specific for therapeutic purpose.
ISSN 24701343
Educational Use Research
Learning Resource Type Article
Publisher Date 2019-05-14
Journal ACS Omega
Volume Number 4
Issue Number 5
Page Count 11
Starting Page 8495
Ending Page 8505