EzCatDB: S00339
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DB codeS00339
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.5.1.34
CSA1dhr

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00329,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109

Enzyme Name
UniProtKBKEGG

P09417P11348
Protein nameDihydropteridine reductaseDihydropteridine reductase6,7-dihydropteridine reductase
6,7-dihydropteridine:NAD(P)H oxidoreductase
DHPR
NAD(P)H:6,7-dihydropteridine oxidoreductase
NADH-dihydropteridine reductase
NADPH-dihydropteridine reductase
NADPH-specific dihydropteridine reductase
dihydropteridine (reduced nicotinamide adenine dinucleotide)reductase
dihydropteridine reductase
dihydropteridine reductase (NADH)
5,6,7,8-tetrahydropteridine:NAD(P)H+ oxidoreductase
SynonymsEC 1.5.1.34
HDHPR
Quinoid dihydropteridine reductase
EC 1.5.1.34
HDHPR
Quinoid dihydropteridine reductase
RefSeqNP_000311.2 (Protein)
NM_000320.2 (DNA/RNA sequence)
NP_071785.1 (Protein)
NM_022390.1 (DNA/RNA sequence)
PfamPF00106 (adh_short)
[Graphical view]
PF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00633Trinitrotoluene degradation
MAP00790Folate biosynthesis

UniProtKB:Accession NumberP09417P11348
Entry nameDHPR_HUMANDHPR_RAT
ActivityA 5,6,7,8-tetrahydropteridine + NAD(P)(+) = a 6,7-dihydropteridine + NAD(P)H.A 5,6,7,8-tetrahydropteridine + NAD(P)(+) = a 6,7-dihydropteridine + NAD(P)H.
SubunitHomodimer.Homodimer.
Subcellular location

Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00272C00003C00006C00268C00080C00004C00005
Compound5,6,7,8-TetrahydrobiopterinNAD+NADP+6,7-DihydrobiopterinH+NADHNADPH
Typeamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateamide group,amine group,nucleotideamide group,amine group,nucleotideamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateothersamide group,amine group,nucleotideamide group,amine group,nucleotide
ChEBI59560
15846
18009

15378
16908
16474
PubChem44257
5893
5886
133246
1038
439153
5884
               
1dhrAUnboundBound:NADUnboundUnbound UnboundUnbound
1dirAUnboundBound:NADUnboundUnbound UnboundUnbound
1dirBUnboundBound:NADUnboundUnbound UnboundUnbound
1dirCUnboundBound:NADUnboundUnbound UnboundUnbound
1dirDUnboundBound:NADUnboundUnbound UnboundUnbound
1hdrAUnboundBound:NADUnboundUnbound UnboundUnbound

Active-site residues
resource
Swiss-prot;P09417, P11348 & literature [15] & [18]
pdbCatalytic residues
         
1dhrATYR 146;LYS 150
1dirATYR 146;LYS 150
1dirBTYR 146;LYS 150
1dirCTYR 146;LYS 150
1dirDTYR 146;LYS 150
1hdrATYR 149;LYS 153

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]Fig.4, p.120
[15]p.5583-5585
[18]Fig.5

references
[1]
PubMed ID3718470
JournalBiochem J
Year1986
Volume234
Pages335-42
AuthorsArmarego WL, Ohnishi A, Taguchi H
TitleNew pteridine substrates for dihydropteridine reductase and horseradish peroxidase.
[2]
PubMed ID3711040
JournalJ Biochem (Tokyo)
Year1986
Volume99
Pages645-52
AuthorsNakanishi N, Hasegawa H, Akino M, Yamada S
TitleCatalytic properties of NADPH-specific dihydropteridine reductase from bovine liver.
[3]
PubMed ID3949795
JournalJ Biol Chem
Year1986
Volume261
Pages3891-3
AuthorsMatthews DA, Webber S, Whiteley JM
TitlePreliminary x-ray diffraction characterization of crystalline rat liver dihydropteridine reductase.
[4]
PubMed ID3569272
JournalEur J Biochem
Year1987
Volume164
Pages403-9
AuthorsArmarego WL, Ohnishi A
TitleInactivation of dihydropteridine reductase (human brain) by platinum(II) complexes.
[5]
PubMed ID3508913
JournalJ Enzyme Inhib
Year1987
Volume1
Pages223-9
AuthorsShen RS, Abell CW
TitleRat striatal synaptosomes as a model system for studying the inhibition of dihydropteridine reductase activity.
[6]
CommentsMUTAGENESIS.
Medline ID91378400
PubMed ID1898002
JournalArch Biochem Biophys
Year1991
Volume287
Pages234-9
AuthorsMatthews DA, Varughese KI, Skinner M, Xuong NH, Hoch J, Trach K, Schneider M, Bray T, Whiteley JM
TitleRole of aspartate-37 in determining cofactor specificity and binding in rat liver dihydropteridine reductase.
Related UniProtKBP11350
[7]
PubMed ID1639779
JournalJ Biol Chem
Year1992
Volume267
Pages15334-9
AuthorsGrimshaw CE, Matthews DA, Varughese KI, Skinner M, Xuong NH, Bray T, Hoch J, Whiteley JM
TitleCharacterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID92335241
PubMed ID1631094
JournalProc Natl Acad Sci U S A
Year1992
Volume89
Pages6080-4
AuthorsVarughese KI, Skinner MM, Whiteley JM, Matthews DA, Xuong NH
TitleCrystal structure of rat liver dihydropteridine reductase.
Related PDB1dhr
Related UniProtKBP11356
[9]
PubMed ID8304094
JournalAdv Exp Med Biol
Year1993
Volume338
Pages123-6
AuthorsVarughese KI, Su Y, Skinner MM, Xuong NH, Matthews DA, Whiteley JM
TitleTwo crystal structures of rat liver dihydropteridine reductase.
[10]
PubMed ID8304093
JournalAdv Exp Med Biol
Year1993
Volume338
Pages115-21
AuthorsWhiteley JM, Xuong NH, Varughese KI
TitleIs dihydropteridine reductase an anomalous dihydrofolate reductase, a flavin-like enzyme, or a short-chain dehydrogenase?
[11]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID94086485
PubMed ID8262916
JournalJ Biol Chem
Year1993
Volume268
Pages26836-41
AuthorsSu Y, Varughese KI, Xuong NH, Bray TL, Roche DJ, Whiteley JM
TitleThe crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue.
Related PDB1hdr
Related UniProtKBP09417
[12]
PubMed ID8433887
JournalPediatr Res
Year1993
Volume33
Pages125-8
AuthorsPonzone A, Guardamagna O, Dianzani I, Ponzone R, Ferrero GB, Spada M, Cotton RG
TitleCatalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment.
[13]
CommentsX-ray crystallography
JournalActa Crystallogr D Biol Crystallogr
Year1994
Volume50
Pages884-8
AuthorsSu Y, Skinner MM, Xuong NH, Matthews DA, Whiteley JM, Varughese KI
TitleCrystal structure of a monoclinic form of dihydropteridine reductase from rat liver.
Related PDB1dir
[14]
PubMed ID7822105
JournalInt J Pept Protein Res
Year1994
Volume44
Pages278-87
AuthorsVarughese KI, Xuong NH, Whiteley JM
TitleStructural and mechanistic implications of incorporating naturally occurring aberrant mutations of human dihydropteridine reductase into a rat model.
[15]
PubMed ID8202530
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages5582-6
AuthorsVarughese KI, Xuong NH, Kiefer PM, Matthews DA, Whiteley JM
TitleStructural and mechanistic characteristics of dihydropteridine reductase: a member of the Tyr-(Xaa)3-Lys-containing family of reductases and dehydrogenases.
[16]
PubMed ID8554609
JournalBiochem Biophys Res Commun
Year1995
Volume217
Pages859-68
AuthorsTsigelny I, Baker ME
TitleStructures stabilizing the dimer interface on human 11 beta-hydroxysteroid dehydrogenase types 1 and 2 and human 15-hydroxyprostaglandin dehydrogenase and their homologs.
[17]
CommentsREVIEW ON VARIANTS.
Medline ID95353277
PubMed ID7627180
JournalHum Mutat
Year1995
Volume5
Pages279-84
AuthorsSmooker PM, Cotton RG
TitleMolecular basis of dihydropteridine reductase deficiency.
Related UniProtKBP09417
[18]
PubMed ID8631945
JournalJ Biol Chem
Year1996
Volume271
Pages3437-44
AuthorsKiefer PM, Varughese KI, Su Y, Xuong NH, Chang CF, Gupta P, Bray T, Whiteley JM
TitleAltered structural and mechanistic properties of mutant dihydropteridine reductases.
[19]
PubMed ID10352712
JournalAdv Exp Med Biol
Year1999
Volume463
Pages403-10
AuthorsChang CF, Bray T, Varughese KI, Whiteley JM
TitleComparative properties of three pteridine reductases.
[20]
CommentsHomologous enzyme
PubMed ID11373620
JournalNat Struct Biol
Year2001
Volume8
Pages521-5
AuthorsGourley DG, Schuttelkopf AW, Leonard GA, Luba J, Hardy LW, Beverley SM, Hunter WN
TitlePteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites.


createdupdated
2003-10-312009-02-26


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