Heat shock protein 90 enhances the electron transfer between the FMN and heme cofactors in neuronal nitric oxide synthase.
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.
['Zheng|Huayu|H|', 'Li|Jinghui|J|', 'Feng|Changjian|C|0000-0003-4542-6497']
D000818:Animals D001224:Aspartic Acid D001665:Binding Sites D003001:Cloning, Molecular D004583:Electrons D004926:Escherichia coli D005362:Ficoll D005486:Flavin Mononucleotide D015870:Gene Expression D005822:Genetic Vectors D018841:HSP90 Heat-Shock Proteins D006418:Heme D006801:Humans D008239:Lysine D062105:Molecular Docking Simulation D009154:Mutation D009249:NADP D052248:Nitric Oxide Synthase Type I D011485:Protein Binding D000072756:Protein Conformation, alpha-Helical D000072757:Protein Conformation, beta-Strand D054730:Protein Interaction Domains and Motifs D051381:Rats D011994:Recombinant Proteins D055672:Static Electricity
heat shock protein 90 electron transfer nitric oxide synthase kinetics docking