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Catalytic Site Atlas

CSA LITERATURE entry for 1dhr

E.C. name6,7-dihydropteridine reductase
SpeciesRattus norvegicus (Rat)
E.C. Number (IntEnz)
CSA Homologues of 1dhr1dir,1hdr,1ooe,
CSA Entries With UniProtID P11348
CSA Entries With EC Number
PDBe Entry 1dhr
PDBSum Entry 1dhr
MACiE Entry 1dhr

Literature Report

IntroductionDihydropteridine reductase catalyses the NADH-mediated reduction of quinoid dihydrobioptertin to give tetrahydrobiopterin, which functions as an essential cofactor in the biosynthetic reactions that convert phenylalanine to tyrosine, tyrosine to dihydroxyphenylalanine and tryptophan to dihydroxytryptophan. These reactions are essential to the generation of the catecholamines. These reactions are found predominantly in nerve, liver and adrenal tissue, where the function of tetrahydrobiopterin has been clearly defined. However, the presence of tetrahydrobiopterin in other tissues is yet to be determined.
MechansimOne possible reduction mechanism first begins with proton transfer from Tyr146 hydroxyl to the substrate carbonyl, followed by rapid hydride transfer to pteridine N(5) position from NADH.

Catalytic Sites for 1dhr

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
LysA150151macie:sideChainThe residue's positively charged side chain influences the pKa of the neighbouring Tyr146 hydroxyl, activating it to act as a general acid to the substrate carbonyl. It is also thought that the residue may act in a proton relay to reprotonate Tyr146 from the solvent through a hydrogen bond to the 2'-hydroxyl of the nicotinamide ring. This interaction orientates the reduced nicotin amide ring such that the pro-S hydrogen is available for transfer to the pteridine N-5 position.
TyrA146147macie:sideChainTyr146 acts as a general acid towards the carbonyl of the dihydroptertidine substrate. It is activated by the presence of the positively charged Lys150, which is also thought to participate in reprotonating Tyr146.

Literature References

Varughese KI
Structural and mechanistic characteristics of dihydropteridine reductase: a member of the Tyr-(Xaa)3-Lys-containing family of reductases and dehydrogenases.
Proc Natl Acad Sci U S A 1994 91 5582-5586
PubMed: 8202530
Filling C
Critical residues for structure and catalysis in short-chain dehydrogenases/reductases.
J Biol Chem 2002 277 25677-25684
PubMed: 11976334