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Unusual folded conformation of nicotinamide adenine dinucleotide bound to flavin reductase P
Author(s) -
Tanner John J.,
Barbour Leonard J.,
Barnes Charles L.,
Tu ShiaoChun,
Krause Kurt L.
Publication year - 1999
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.8.9.1725
Subject(s) - nad+ kinase , cofactor , flavin group , nicotinamide adenine dinucleotide , stereochemistry , chemistry , nicotinamide , reductase , glycerol 3 phosphate dehydrogenase , flavin adenine dinucleotide , enzyme , biochemistry
The 2.1 Å resolution crystal structure of flavin reductase P with the inhibitor nicotinamide adenine dinucleotide (NAD) bound in the active site has been determined. NAD adopts a novel, folded conformation in which the nicotinamide and adenine rings stack in parallel with an inter‐ring distance of 3.6 Å. The pyrophosphate binds next to the flavin cofactor isoalloxazine, while the stacked nicotinamide/adenine moiety faces away from the flavin. The observed NAD conformation is quite different from the extended conformations observed in other enzyme/NAD (P) structures; however, it resembles the conformation proposed for NAD in solution. The flavin reductase P/NAD structure provides new information about the conformational diversity of NAD, which is important for understanding catalysis. This structure offers the first crystallographic evidence of a folded NAD with ring stacking, and it is the first enzyme structure containing an FMN cofactor interacting with NAD(P). Analysis of the structure suggests a possible dynamic mechanism underlying NADPH substrate specificity and product release that involves unfolding and folding of NADP(H).