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| - | [[Image:1hdr.gif|left|200px]] | |
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| - | {{Structure
| + | ==THE CRYSTALLOGRAPHIC STRUCTURE OF A HUMAN DIHYDROPTERIDINE REDUCTASE NADH BINARY COMPLEX EXPRESSED IN ESCHERICHIA COLI BY A CDNA CONSTRUCTED FROM ITS RAT HOMOLOGUE== |
| - | |PDB= 1hdr |SIZE=350|CAPTION= <scene name='initialview01'>1hdr</scene>, resolution 2.5Å
| + | <StructureSection load='1hdr' size='340' side='right'caption='[[1hdr]], [[Resolution|resolution]] 2.50Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>
| + | <table><tr><td colspan='2'>[[1hdr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HDR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HDR FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/6,7-dihydropteridine_reductase 6,7-dihydropteridine reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.34 1.5.1.34] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | |GENE= CDNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hdr OCA], [https://pdbe.org/1hdr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hdr RCSB], [https://www.ebi.ac.uk/pdbsum/1hdr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hdr ProSAT]</span></td></tr> |
| - | |RELATEDENTRY= | + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hdr OCA], [http://www.ebi.ac.uk/pdbsum/1hdr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hdr RCSB]</span>
| + | == Disease == |
| - | }}
| + | [https://www.uniprot.org/uniprot/DHPR_HUMAN DHPR_HUMAN] Defects in QDPR are the cause of BH4-deficient hyperphenylalaninemia type C (HPABH4C) [MIM:[https://omim.org/entry/261630 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.<ref>PMID:9744478</ref> <ref>PMID:8326489</ref> <ref>PMID:2116088</ref> <ref>PMID:10408783</ref> <ref>PMID:11153907</ref> |
| - | | + | == Function == |
| - | '''THE CRYSTALLOGRAPHIC STRUCTURE OF A HUMAN DIHYDROPTERIDINE REDUCTASE NADH BINARY COMPLEX EXPRESSED IN ESCHERICHIA COLI BY A CDNA CONSTRUCTED FROM ITS RAT HOMOLOGUE'''
| + | [https://www.uniprot.org/uniprot/DHPR_HUMAN DHPR_HUMAN] The product of this enzyme, tetrahydrobiopterin (BH-4), is an essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases. |
| - | | + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | ==Overview== | + | Check<jmol> |
| - | A human dihydropteridine reductase (EC 1.6.99.10) has been created from a rat cDNA clone by a single five-oligonucleotide mutagenesis reaction and expressed in good yield in Escherichia coli. The enzyme has been purified to homogeneity, and kinetic identity to the naturally occurring enzyme has been proven. Crystallization has also been achieved, and the crystal structure was solved using 2.5 A data that was refined to an R value of 16.9%. The structure described in this report represents the first complete structural characterization of this important human enzyme.
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/1hdr_consurf.spt"</scriptWhenChecked> |
| - | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | 1HDR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HDR OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==Reference== | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hdr ConSurf]. |
| - | The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue., Su Y, Varughese KI, Xuong NH, Bray TL, Roche DJ, Whiteley JM, J Biol Chem. 1993 Dec 25;268(36):26836-41. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8262916 8262916]
| + | <div style="clear:both"></div> |
| - | [[Category: 6,7-dihydropteridine reductase]]
| + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Su, Y.]] | + | [[Category: Su Y]] |
| - | [[Category: Varughese, K I.]] | + | [[Category: Varughese KI]] |
| - | [[Category: Whiteley, J M.]] | + | [[Category: Whiteley JM]] |
| - | [[Category: Xuong, N H.]] | + | [[Category: Xuong NH]] |
| - | [[Category: oxidoreductase(acting on nadh)]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:03:03 2008''
| + | |
| Structural highlights
Disease
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
- ↑ Smooker PM, Gough TJ, Cotton RG, Alliaudi C, de Sanctis L, Dianzani I. A series of mutations in the dihydropteridine reductase gene resulting in either abnormal RNA splicing or DHPR protein defects. Mutations in brief no. 244. Online. Hum Mutat. 1999;13(6):503-4. PMID:10408783 doi:<503::AID-HUMU13>3.0.CO;2-F 10.1002/(SICI)1098-1004(1999)13:6<503::AID-HUMU13>3.0.CO;2-F
- ↑ 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
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