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Title: Building on a theme: The redox hierarchy of pyridine nucleotide-disulfide oxidoreductases
Flavin disulfide reductases (FDRs) are FAD-dependent enzymes that transmit electrons from NAD(P)H to reduce specific oxidant substrate disulfides. These enzymes have been studied extensively, most particularly the paradigm examples: glutathione reductase and thioredoxin reductase. The common, though not universal, traits of the family include a tyrosine- or phenylalanine-gated binding pocket for NAD(P) nicotinamides adjacent to the FAD isoalloxazine re-face, and a disulfide stacked against the si-face of the isoalloxazine whose dithiol form is activated for subsequent exchange reactions by a nearby histidine acting as a base. This arrangement promotes transduction of the reducing equivalents for disulfide exchange relay reactions. From an observational standpoint the proximal parallel stacking of three redox moieties induces up to three opportunities for unique charge transfer interactions (NAD(P)H FAD, NAD(P)+•FADH2, and FAD•thiolate). In transient state, the charge transfer transitions provide discrete signals to assign reaction sequences. This review summarizes the lineage of observations for the FDR enzymes that have been extensively studied. Where applicable and in order to chart a consistent interpretation of the record, only data derived from studies that used anaerobic methods are cited. These data reveal a recurring theme for catalysis that is elaborated with specific additional functionalities for each oxidant substrate.  more » « less
Award ID(s):
2203593
NSF-PAR ID:
10517102
Author(s) / Creator(s):
;
Corporate Creator(s):
Editor(s):
Jin, Jian-Ping; Forman, Henry
Publisher / Repository:
Elsivier
Date Published:
Journal Name:
Archives of Biochemistry and Biophysics
Volume:
755
Issue:
C
ISSN:
0003-9861
Page Range / eLocation ID:
109966
Subject(s) / Keyword(s):
flavoprotein transient kinetics disulfide, reductase, thioredoxin glutathione
Format(s):
Medium: X Size: N/A Other: N/A
Size(s):
N/A
Sponsoring Org:
National Science Foundation
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