THE CRYSTALLOGRAPHIC STRUCTURE OF A HUMAN DIHYDROPTERIDINE REDUCTASE NADH BINARY COMPLEX EXPRESSED IN ESCHERICHIA COLI BY A CDNA CONSTRUCTED FROM ITS RAT HOMOLOGUE
1hdr is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
DHPR_HUMAN Defects in QDPR are the cause of BH4-deficient hyperphenylalaninemia type C (HPABH4C) [MIM:261630; also called dihydropteridine reductase deficiency (DHPR deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to DHPR deficiency or quinoid dihydropteridine reductase deficiency (QDPR deficiency). HPABH4C is a rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. These patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated.[1][2][3][4][5]
Function
DHPR_HUMAN The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
↑Dianzani I, de Sanctis L, Smooker PM, Gough TJ, Alliaudi C, Brusco A, Spada M, Blau N, Dobos M, Zhang HP, Yang N, Ponzone A, Armarego WL, Cotton RG. Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Hum Mutat. 1998;12(4):267-73. PMID:9744478 doi:<267::AID-HUMU8>3.0.CO;2-C 10.1002/(SICI)1098-1004(1998)12:4<267::AID-HUMU8>3.0.CO;2-C
↑Dianzani I, Howells DW, Ponzone A, Saleeba JA, Smooker PM, Cotton RG. Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency. J Med Genet. 1993 Jun;30(6):465-9. PMID:8326489
↑Howells DW, Forrest SM, Dahl HH, Cotton RG. Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency. Am J Hum Genet. 1990 Aug;47(2):279-85. PMID:2116088
↑Romstad A, Kalkanoglu HS, Coskun T, Demirkol M, Tokatli A, Dursun A, Baykal T, Ozalp I, Guldberg P, Guttler F. Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE). Hum Genet. 2000 Dec;107(6):546-53. PMID:11153907
