DB code: S00339

CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.5.1.34
CSA 1dhr
M-CSA 1dhr
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P09417 Dihydropteridine reductase
EC 1.5.1.34
HDHPR
Quinoid dihydropteridine reductase
NP_000311.2 (Protein)
NM_000320.2 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]
P11348 Dihydropteridine reductase
EC 1.5.1.34
HDHPR
Quinoid dihydropteridine reductase
NP_071785.1 (Protein)
NM_022390.1 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]

KEGG enzyme name
6,7-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P09417 DHPR_HUMAN A 5,6,7,8-tetrahydropteridine + NAD(P)(+) = a 6,7-dihydropteridine + NAD(P)H. Homodimer.
P11348 DHPR_RAT A 5,6,7,8-tetrahydropteridine + NAD(P)(+) = a 6,7-dihydropteridine + NAD(P)H. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00633 Trinitrotoluene degradation
MAP00790 Folate biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C00272 C00003 C00006 C00268 C00080 C00004 C00005
E.C.
Compound 5,6,7,8-Tetrahydrobiopterin NAD+ NADP+ 6,7-Dihydrobiopterin H+ NADH NADPH
Type amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate amide group,amine group,nucleotide amide group,amine group,nucleotide amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate others amide group,amine group,nucleotide amide group,amine group,nucleotide
ChEBI 59560
 59560
 		15846
 15846
 		18009
 18009
 		15378
 15378
 		16908
 16908
 		16474
 16474
PubChem 44257
 44257
 		5893
 5893
 		5886
 5886
 		133246
 133246
 		1038
 1038
 		439153
 439153
 		5884
 5884
1dhrA Unbound Bound:NAD Unbound Unbound Unbound Unbound
1dirA Unbound Bound:NAD Unbound Unbound Unbound Unbound
1dirB Unbound Bound:NAD Unbound Unbound Unbound Unbound
1dirC Unbound Bound:NAD Unbound Unbound Unbound Unbound
1dirD Unbound Bound:NAD Unbound Unbound Unbound Unbound
1hdrA Unbound Bound:NAD Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P09417, P11348 & literature [15] & [18]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dhrA TYR 146;LYS 150
1dirA TYR 146;LYS 150
1dirB TYR 146;LYS 150
1dirC TYR 146;LYS 150
1dirD TYR 146;LYS 150
1hdrA TYR 149;LYS 153

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
Fig.4, p.120
[15]
p.5583-5585
[18]
Fig.5

References
[1]
Resource
Comments
Medline ID
PubMed ID 3718470
Journal Biochem J
Year 1986
Volume 234
Pages 335-42
Authors Armarego WL, Ohnishi A, Taguchi H
Title New pteridine substrates for dihydropteridine reductase and horseradish peroxidase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3711040
Journal J Biochem (Tokyo)
Year 1986
Volume 99
Pages 645-52
Authors Nakanishi N, Hasegawa H, Akino M, Yamada S
Title Catalytic properties of NADPH-specific dihydropteridine reductase from bovine liver.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3949795
Journal J Biol Chem
Year 1986
Volume 261
Pages 3891-3
Authors Matthews DA, Webber S, Whiteley JM
Title Preliminary x-ray diffraction characterization of crystalline rat liver dihydropteridine reductase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3569272
Journal Eur J Biochem
Year 1987
Volume 164
Pages 403-9
Authors Armarego WL, Ohnishi A
Title Inactivation of dihydropteridine reductase (human brain) by platinum(II) complexes.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3508913
Journal J Enzyme Inhib
Year 1987
Volume 1
Pages 223-9
Authors Shen RS, Abell CW
Title Rat striatal synaptosomes as a model system for studying the inhibition of dihydropteridine reductase activity.
Related PDB
Related UniProtKB
[6]
Resource
Comments MUTAGENESIS.
Medline ID 91378400
PubMed ID 1898002
Journal Arch Biochem Biophys
Year 1991
Volume 287
Pages 234-9
Authors Matthews DA, Varughese KI, Skinner M, Xuong NH, Hoch J, Trach K, Schneider M, Bray T, Whiteley JM
Title Role of aspartate-37 in determining cofactor specificity and binding in rat liver dihydropteridine reductase.
Related PDB
Related UniProtKB P11350
[7]
Resource
Comments
Medline ID
PubMed ID 1639779
Journal J Biol Chem
Year 1992
Volume 267
Pages 15334-9
Authors Grimshaw CE, Matthews DA, Varughese KI, Skinner M, Xuong NH, Bray T, Hoch J, Whiteley JM
Title Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 92335241
PubMed ID 1631094
Journal Proc Natl Acad Sci U S A
Year 1992
Volume 89
Pages 6080-4
Authors Varughese KI, Skinner MM, Whiteley JM, Matthews DA, Xuong NH
Title Crystal structure of rat liver dihydropteridine reductase.
Related PDB 1dhr
Related UniProtKB P11356
[9]
Resource
Comments
Medline ID
PubMed ID 8304094
Journal Adv Exp Med Biol
Year 1993
Volume 338
Pages 123-6
Authors Varughese KI, Su Y, Skinner MM, Xuong NH, Matthews DA, Whiteley JM
Title Two crystal structures of rat liver dihydropteridine reductase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8304093
Journal Adv Exp Med Biol
Year 1993
Volume 338
Pages 115-21
Authors Whiteley JM, Xuong NH, Varughese KI
Title Is dihydropteridine reductase an anomalous dihydrofolate reductase, a flavin-like enzyme, or a short-chain dehydrogenase?
Related PDB
Related UniProtKB
[11]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 94086485
PubMed ID 8262916
Journal J Biol Chem
Year 1993
Volume 268
Pages 26836-41
Authors Su Y, Varughese KI, Xuong NH, Bray TL, Roche DJ, Whiteley JM
Title The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue.
Related PDB 1hdr
Related UniProtKB P09417
[12]
Resource
Comments
Medline ID
PubMed ID 8433887
Journal Pediatr Res
Year 1993
Volume 33
Pages 125-8
Authors Ponzone A, Guardamagna O, Dianzani I, Ponzone R, Ferrero GB, Spada M, Cotton RG
Title Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID
Journal Acta Crystallogr D Biol Crystallogr
Year 1994
Volume 50
Pages 884-8
Authors Su Y, Skinner MM, Xuong NH, Matthews DA, Whiteley JM, Varughese KI
Title Crystal structure of a monoclinic form of dihydropteridine reductase from rat liver.
Related PDB 1dir
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7822105
Journal Int J Pept Protein Res
Year 1994
Volume 44
Pages 278-87
Authors Varughese KI, Xuong NH, Whiteley JM
Title Structural and mechanistic implications of incorporating naturally occurring aberrant mutations of human dihydropteridine reductase into a rat model.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8202530
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 5582-6
Authors Varughese KI, Xuong NH, Kiefer PM, Matthews DA, Whiteley JM
Title Structural and mechanistic characteristics of dihydropteridine reductase: a member of the Tyr-(Xaa)3-Lys-containing family of reductases and dehydrogenases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8554609
Journal Biochem Biophys Res Commun
Year 1995
Volume 217
Pages 859-68
Authors Tsigelny I, Baker ME
Title Structures stabilizing the dimer interface on human 11 beta-hydroxysteroid dehydrogenase types 1 and 2 and human 15-hydroxyprostaglandin dehydrogenase and their homologs.
Related PDB
Related UniProtKB
[17]
Resource
Comments REVIEW ON VARIANTS.
Medline ID 95353277
PubMed ID 7627180
Journal Hum Mutat
Year 1995
Volume 5
Pages 279-84
Authors Smooker PM, Cotton RG
Title Molecular basis of dihydropteridine reductase deficiency.
Related PDB
Related UniProtKB P09417
[18]
Resource
Comments
Medline ID
PubMed ID 8631945
Journal J Biol Chem
Year 1996
Volume 271
Pages 3437-44
Authors Kiefer PM, Varughese KI, Su Y, Xuong NH, Chang CF, Gupta P, Bray T, Whiteley JM
Title Altered structural and mechanistic properties of mutant dihydropteridine reductases.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10352712
Journal Adv Exp Med Biol
Year 1999
Volume 463
Pages 403-10
Authors Chang CF, Bray T, Varughese KI, Whiteley JM
Title Comparative properties of three pteridine reductases.
Related PDB
Related UniProtKB
[20]
Resource
Comments Homologous enzyme
Medline ID
PubMed ID 11373620
Journal Nat Struct Biol
Year 2001
Volume 8
Pages 521-5
Authors Gourley DG, Schuttelkopf AW, Leonard GA, Luba J, Hardy LW, Beverley SM, Hunter WN
Title Pteridine reductase mechanism correlates pterin metabolism with drug resistance in trypanosomatid parasites.
Related PDB
Related UniProtKB

Comments

Created Updated
2003-10-31 2009-02-26