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- W2938962921 abstract "(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitor to the loop5/α2/α3 allosteric pocket. Molecular dynamics simulations were carried out for 100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP-S-trityl-l-cysteine (Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP), Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyses were done using Umbrella sampling, Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities. The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our data strongly support a stable Eg5-MF complex, with significantly low binding energy and reduced flexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 was trapped in a downward position to keep the allosteric pocket of Eg5 in the so-called “closed conformation”, comparable to observations for STLC. Altered structural conformations were also visible within various regions of Eg5, including switch I, switch II, α2/α3 helices, and the tubulin-binding region, indicating that MF might induce modifications in the Eg5 structure to compromise its ATP/ADP binding and conversion process as well as its interaction with microtubules. The described mechanisms are crucial for understanding Eg5 inhibition by MF." @default.
- W2938962921 created "2019-04-25" @default.
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- W2938962921 date "2019-04-16" @default.
- W2938962921 modified "2023-10-16" @default.
- W2938962921 title "Insights into the Molecular Mechanisms of Eg5 Inhibition by (+)-Morelloflavone" @default.
- W2938962921 cites W1828461598 @default.
- W2938962921 cites W1883224873 @default.
- W2938962921 cites W1949283845 @default.
- W2938962921 cites W1964258277 @default.
- W2938962921 cites W1966078827 @default.
- W2938962921 cites W1966680971 @default.
- W2938962921 cites W1969836007 @default.
- W2938962921 cites W1987280449 @default.
- W2938962921 cites W1995289937 @default.
- W2938962921 cites W2001219990 @default.
- W2938962921 cites W2006069089 @default.
- W2938962921 cites W2009018090 @default.
- W2938962921 cites W2013754612 @default.
- W2938962921 cites W2016986564 @default.
- W2938962921 cites W2017196167 @default.
- W2938962921 cites W2020270227 @default.
- W2938962921 cites W2022203086 @default.
- W2938962921 cites W2027861315 @default.
- W2938962921 cites W2029073568 @default.
- W2938962921 cites W2029667189 @default.
- W2938962921 cites W2030701627 @default.
- W2938962921 cites W2033334357 @default.
- W2938962921 cites W2037535298 @default.
- W2938962921 cites W2039949136 @default.
- W2938962921 cites W2043812489 @default.
- W2938962921 cites W2044172327 @default.
- W2938962921 cites W2044819384 @default.
- W2938962921 cites W2045518803 @default.
- W2938962921 cites W2046546361 @default.
- W2938962921 cites W2052132055 @default.
- W2938962921 cites W2052309340 @default.
- W2938962921 cites W2052453216 @default.
- W2938962921 cites W2057523896 @default.
- W2938962921 cites W2060018494 @default.
- W2938962921 cites W2061272721 @default.
- W2938962921 cites W2062121686 @default.
- W2938962921 cites W2067174909 @default.
- W2938962921 cites W2069123478 @default.
- W2938962921 cites W2071380080 @default.
- W2938962921 cites W2072540184 @default.
- W2938962921 cites W2074338059 @default.
- W2938962921 cites W2075172702 @default.
- W2938962921 cites W2081693079 @default.
- W2938962921 cites W2081721965 @default.
- W2938962921 cites W2082335806 @default.
- W2938962921 cites W2091547089 @default.
- W2938962921 cites W2128572087 @default.
- W2938962921 cites W2130479394 @default.
- W2938962921 cites W2132629607 @default.
- W2938962921 cites W2133492742 @default.
- W2938962921 cites W2134967712 @default.
- W2938962921 cites W2147993766 @default.
- W2938962921 cites W2153527953 @default.
- W2938962921 cites W2155004688 @default.
- W2938962921 cites W2160310346 @default.
- W2938962921 cites W2161605421 @default.
- W2938962921 cites W2168240189 @default.
- W2938962921 cites W2171268876 @default.
- W2938962921 cites W2313646154 @default.
- W2938962921 cites W2325423092 @default.
- W2938962921 cites W2401546034 @default.
- W2938962921 cites W2409095409 @default.
- W2938962921 cites W2479078614 @default.
- W2938962921 cites W2510180940 @default.
- W2938962921 cites W2548754181 @default.
- W2938962921 cites W2565946295 @default.
- W2938962921 cites W2587285633 @default.
- W2938962921 cites W2605672998 @default.
- W2938962921 cites W2610760221 @default.
- W2938962921 cites W2690502449 @default.
- W2938962921 cites W2792897273 @default.
- W2938962921 cites W2804822363 @default.
- W2938962921 cites W2883555544 @default.
- W2938962921 cites W2915130973 @default.
- W2938962921 doi "https://doi.org/10.3390/ph12020058" @default.
- W2938962921 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6630617" @default.
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- W2938962921 hasPublicationYear "2019" @default.
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