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Heat shock protein 90 enhances the electron transfer between the FMN and heme cofactors in neuronal nitric oxide synthase
Author(s) -
Zheng Huayu,
Li Jinghui,
Feng Changjian
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13870
Subject(s) - hsp90 , heme , nitric oxide synthase , chemistry , heat shock protein , cofactor , nitric oxide , biophysics , biochemistry , atp synthase , cytosol , hemeprotein , biology , enzyme , organic chemistry , gene
Heat shock protein 90 (Hsp90) is a key regulator of nitric oxide synthase (NOS) in vivo . Despite its functional importance, little is known about the underlying molecular mechanism. Here, purified dimeric human Hsp90α was used to investigate whether (and if so, how) Hsp90 affects the FMN–heme interdomain electron transfer (IET) step in NOS. Hsp90α increases the IET rate for rat neuronal NOS (nNOS) in a dose‐saturable manner, and a single charge‐neutralization mutation at conserved Hsp90 K585 abolishes the effect. The kinetic results with added Ficoll 70, a crowder, further indicate that Hsp90 enhances the FMN–heme IET through specific association with nNOS. The Hsp90‐nNOS docking models provide hints on the putative role of Hsp90 in constraining the available conformational space for the FMN domain motions.