1dmw

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CRYSTAL STRUCTURE OF DOUBLE TRUNCATED HUMAN PHENYLALANINE HYDROXYLASE WITH BOUND 7,8-DIHYDRO-L-BIOPTERIN

Structural highlights

1dmw is a 1 chain structure with sequence from Homo sapiens. The January 2005 RCSB PDB Molecule of the Month feature on Phenylalanine Hydroxylase by Shuchismita Dutta and David S. Goodsell is 10.2210/rcsb_pdb/mom_2005_1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1pah, 2pah, 3pah, 4pah, 5pah, 6pah
Activity:	Phenylalanine 4-monooxygenase, with EC number 1.14.16.1
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[PH4H_HUMAN] Defects in PAH are the cause of phenylketonuria (PKU) [MIM:261600]. PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] ^[19] ^[20] ^[21] ^[22] ^[23] ^[24] ^[25] ^[26] ^[27] ^[28] ^[29] ^[30] ^[31] ^[32] ^[33] ^[34] ^[35] ^[36] ^[37] ^[38] Defects in PAH are the cause of non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:261600]. Non-PKU HPA is a mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one. Defects in PAH are the cause of hyperphenylalaninemia (HPA) [MIM:261600]. HPA is the mildest form of phenylalanine hydroxylase deficiency.^[39] ^[40] ^[41] ^[42] ^[43] ^[44] ^[45] ^[46]

Function

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of the dimeric catalytic domain (residues 118-424) of human PheOH (hPheOH), cocrystallized with the oxidized form of the cofactor (7,8-dihydro-L-biopterin, BH(2)), has been determined at 2.0 A resolution. The pterin binds in the second coordination sphere of the catalytic iron (the C4a atom is 6.1 A away), and interacts through several hydrogen bonds to two water molecules coordinated to the iron, as well as to the main chain carbonyl oxygens of Ala322, Gly247, and Leu249 and the main chain amide of Leu249. Some important conformational changes are seen in the active site upon pterin binding. The loop between residues 245 and 250 moves in the direction of the iron, and thus allows for several important hydrogen bonds to the pterin ring to be formed. The pterin cofactor is in an ideal orientation for dioxygen to bind in a bridging position between the iron and the pterin. The pterin ring forms an aromatic pi-stacking interaction with Phe254, and Tyr325 contributes to the positioning of the pterin ring and its dihydroxypropyl side chain by hydrophobic interactions. Of particular interest in the hPheOH x BH(2) binary complex structure is the finding that Glu286 hydrogen bonds to one of the water molecules coordinated to the iron as well as to a water molecule which hydrogen bonds to N3 of the pterin ring. Site-specific mutations of Glu286 (E286A and E286Q), Phe254 (F254A and F254L), and Tyr325 (Y325F) have confirmed the important contribution of Glu286 and Phe254 to the normal positioning of the pterin cofactor and catalytic activity of hPheOH. Tyr325 also contributes to the correct positioning of the pterin, but has no direct function in the catalytic reaction, in agreement with the results obtained with rat TyrOH [Daubner, S. C., and Fitzpatrick, P. F. (1998) Biochemistry 37, 16440-16444]. Superposition of the binary hPheOH.BH(2) complex onto the crystal structure of the ligand-free rat PheOH (which contains the regulatory and catalytic domains) [Kobe, B., Jennings, I. G., House, C. M., Michell, B. J., Goodwill, K. E., Santarsiero, B. D., Stevens, R. C., Cotton, R. G. H., and Kemp, B. E. (1999) Nat. Struct. Biol. 6, 442-448] reveals that the C2'-hydroxyl group of BH(2) is sufficiently close to form hydrogen bonds to Ser23 in the regulatory domain. Similar interactions are seen with the hPheOH.adrenaline complex and Ser23. These interactions suggest a structural explanation for the specific regulatory properties of the dihydroxypropyl side chain of BH(4) (negative effector) in the full-length enzyme in terms of phosphorylation of Ser16 and activation by L-Phe.

Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase.,Erlandsen H, Bjorgo E, Flatmark T, Stevens RC Biochemistry. 2000 Mar 7;39(9):2208-17. PMID:10694386^[47]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hoang L, Byck S, Prevost L, Scriver CR. PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus. Nucleic Acids Res. 1996 Jan 1;24(1):127-31. PMID:8594560
↑ Lichter-Konecki U, Konecki DS, DiLella AG, Brayton K, Marvit J, Hahn TM, Trefz FK, Woo SL. Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene. Biochemistry. 1988 Apr 19;27(8):2881-5. PMID:2840952
↑ Lyonnet S, Caillaud C, Rey F, Berthelon M, Frezal J, Rey J, Munnich A. Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency. Am J Hum Genet. 1989 Apr;44(4):511-7. PMID:2564729
↑ Hofman KJ, Antonarakis SE, Missiou-Tsangaraki S, Boehm CD, Valle D. Phenylketonuria in the Greek population. Haplotype analysis of the phenylalanine hydroxylase gene and identification of a PKU mutation. Mol Biol Med. 1989 Jun;6(3):245-50. PMID:2615649
↑ Svensson E, Andersson B, Hagenfeldt L. Two mutations within the coding sequence of the phenylalanine hydroxylase gene. Hum Genet. 1990 Aug;85(3):300-4. PMID:1975559
↑ Dianzani I, Forrest SM, Camaschella C, Saglio G, Ponzone A, Cotton RG. Screening for mutations in the phenylalanine hydroxylase gene from Italian patients with phenylketonuria by using the chemical cleavage method: a new splice mutation. Am J Hum Genet. 1991 Mar;48(3):631-5. PMID:1671810
↑ Hofman KJ, Steel G, Kazazian HH, Valle D. Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. Am J Hum Genet. 1991 Apr;48(4):791-8. PMID:2014802
↑ Okano Y, Wang T, Eisensmith RC, Longhi R, Riva E, Giovannini M, Cerone R, Romano C, Woo SL. Phenylketonuria missense mutations in the Mediterranean. Genomics. 1991 Jan;9(1):96-103. PMID:1672294
↑ Dworniczak B, Grudda K, Stumper J, Bartholome K, Aulehla-Scholz C, Horst J. Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria. Genomics. 1991 Jan;9(1):193-9. PMID:1672290
↑ Konecki DS, Schlotter M, Trefz FK, Lichter-Konecki U. The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria. Hum Genet. 1991 Aug;87(4):389-93. PMID:1679030
↑ Caillaud C, Lyonnet S, Rey F, Melle D, Frebourg T, Berthelon M, Vilarinho L, Vaz Osorio R, Rey J, Munnich A. A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. J Biol Chem. 1991 May 25;266(15):9351-4. PMID:1709636
↑ Lin CH, Hsiao KJ, Tsai TF, Chao HK, Su TS. Identification of a missense phenylketonuria mutation at codon 408 in Chinese. Hum Genet. 1992 Aug;89(6):593-6. PMID:1355066
↑ Jaruzelska J, Melle D, Matuszak R, Borski K, Munnich A. A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mol Genet. 1992 Dec;1(9):763-4. PMID:1363837
↑ Desviat LR, Perez B, Ugarte M. A new PKU mutation associated with haplotype 12. Hum Mol Genet. 1992 Dec;1(9):765-6. PMID:1363838
↑ Guldberg P, Henriksen KF, Guttler F. Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis. Genomics. 1993 Jul;17(1):141-6. PMID:8406445 doi:http://dx.doi.org/10.1006/geno.1993.1295
↑ Goebel-Schreiner B, Schreiner R. Identification of a new missense mutation in Japanese phenylketonuric patients. J Inherit Metab Dis. 1993;16(6):950-6. PMID:8068076
↑ Benit P, Rey F, Melle D, Munnich A, Rey J. Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mutat. 1994;4(3):229-31. PMID:7833954 doi:http://dx.doi.org/10.1002/humu.1380040311
↑ Knappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T. PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems. Hum Mutat. 1996;8(3):236-46. PMID:8889583 doi:<236::AID-HUMU7>3.0.CO;2-7 10.1002/(SICI)1098-1004(1996)8:3<236::AID-HUMU7>3.0.CO;2-7
↑ Guldberg P, Mallmann R, Henriksen KF, Guttler F. Phenylalanine hydroxylase deficiency in a population in Germany: mutational profile and nine novel mutations. Hum Mutat. 1996;8(3):276-9. PMID:8889590 doi:<276::AID-HUMU14>3.0.CO;2-# 10.1002/(SICI)1098-1004(1996)8:3<276::AID-HUMU14>3.0.CO;2-#
↑ Argiolas A, Bosco P, Cali F, Ceratto N, Anello G, Riva E, Biasucci G, Carducci C, Romano V. Two novel PAH gene mutations detected in Italian phenylketonuric patients. Hum Genet. 1997 Feb;99(2):275-8. PMID:9048935
↑ Byck S, Tyfield L, Carter K, Scriver CR. Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations. Hum Mutat. 1997;9(4):316-21. PMID:9101291 doi:<316::AID-HUMU3>3.0.CO;2-3 10.1002/(SICI)1098-1004(1997)9:4<316::AID-HUMU3>3.0.CO;2-3
↑ Bosco P, Cali F, Meli C, Mollica F, Zammarchi E, Cerone R, Vanni C, Palillo L, Greco D, Romano V. Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia. Hum Mutat. 1998;11(3):240-3. PMID:9521426 doi:<240::AID-HUMU9>3.0.CO;2-L 10.1002/(SICI)1098-1004(1998)11:3<240::AID-HUMU9>3.0.CO;2-L
↑ De Lucca M, Perez B, Desviat LR, Ugarte M. Molecular basis of phenylketonuria in Venezuela: presence of two novel null mutations. Hum Mutat. 1998;11(5):354-9. PMID:9600453 doi:<354::AID-HUMU2>3.0.CO;2-W 10.1002/(SICI)1098-1004(1998)11:5<354::AID-HUMU2>3.0.CO;2-W
↑ Mallolas J, Campistol J, Lambruschini N, Vilaseca MA, Cambra FJ, Estivill X, Mila M. Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online. Hum Mutat. 1998;11(6):482. PMID:10200057 doi:<482::AID-HUMU14>3.0.CO;2-H 10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU14>3.0.CO;2-H
↑ Park YS, Seoung CS, Lee SW, Oh KH, Lee DH, Yim J. Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X. Hum Mutat. 1998;Suppl 1:S121-2. PMID:9452061
↑ Michiels L, Francois B, Raus J, Vandevyver C. Identification of seven new mutations in the phenylalanine hydroxylase gene, associated with hyperphenylalaninemia in the Belgian population. Hum Mutat. 1998;Suppl 1:S123-4. PMID:9452062
↑ Popescu T, Blazkova M, Kozak L, Jebeleanu G, Popescu A. Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles. Hum Mutat. 1998;12(5):314-9. PMID:9792407 doi:<314::AID-HUMU4>3.0.CO;2-D 10.1002/(SICI)1098-1004(1998)12:5<314::AID-HUMU4>3.0.CO;2-D
↑ Waters PJ, Parniak MA, Hewson AS, Scriver CR. Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH). Hum Mutat. 1998;12(5):344-54. PMID:9792411 doi:<344::AID-HUMU8>3.0.CO;2-D 10.1002/(SICI)1098-1004(1998)12:5<344::AID-HUMU8>3.0.CO;2-D
↑ Corsello G, Bosco P, Cali F, Greco D, Cammarata M, Ciaccio M, Piccione M, Romano V. Maternal phenylketonuria in two Sicilian families identified by maternal blood phenylalanine level screening and identification of a new phenylalanine hydroxylase gene mutation (P407L) Eur J Pediatr. 1999 Jan;158(1):83-4. PMID:9950317
↑ Hennermann JB, Vetter B, Wolf C, Windt E, Buhrdel P, Seidel J, Monch E, Kulozik AE. Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations. Hum Mutat. 2000;15(3):254-60. PMID:10679941 doi:<254::AID-HUMU6>3.0.CO;2-W 10.1002/(SICI)1098-1004(200003)15:3<254::AID-HUMU6>3.0.CO;2-W
↑ Gjetting T, Petersen M, Guldberg P, Guttler F. Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. Am J Hum Genet. 2001 Jun;68(6):1353-60. Epub 2001 Apr 20. PMID:11326337 doi:S0002-9297(07)61046-5
↑ Acosta A, Silva W Jr, Carvalho T, Gomes M, Zago M. Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria. Hum Mutat. 2001 Feb;17(2):122-30. PMID:11180595 doi:<122::AID-HUMU4>3.0.CO;2-C 10.1002/1098-1004(200102)17:2<122::AID-HUMU4>3.0.CO;2-C
↑ Yang Y, Drummond-Borg M, Garcia-Heras J. Molecular analysis of phenylketonuria (PKU) in newborns from Texas. Hum Mutat. 2001 Jun;17(6):523. PMID:11385716 doi:10.1002/humu.1141
↑ Gjetting T, Romstad A, Haavik J, Knappskog PM, Acosta AX, Silva WA Jr, Zago MA, Guldberg P, Guttler F. A phenylalanine hydroxylase amino acid polymorphism with implications for molecular diagnostics. Mol Genet Metab. 2001 Jul;73(3):280-4. PMID:11461196 doi:10.1006/mgme.2001.3180
↑ Muntau AC, Roschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA. Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N Engl J Med. 2002 Dec 26;347(26):2122-32. PMID:12501224 doi:10.1056/NEJMoa021654
↑ Gersting SW, Kemter KF, Staudigl M, Messing DD, Danecka MK, Lagler FB, Sommerhoff CP, Roscher AA, Muntau AC. Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. Am J Hum Genet. 2008 Jul;83(1):5-17. doi: 10.1016/j.ajhg.2008.05.013. Epub 2008, Jun 5. PMID:18538294 doi:10.1016/j.ajhg.2008.05.013
↑ Sterl E, Paul K, Paschke E, Zschocke J, Brunner-Krainz M, Windisch E, Konstantopoulou V, Moslinger D, Karall D, Scholl-Burgi S, Sperl W, Lagler F, Plecko B. Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among Austrian patients with PAH deficiency: comprehensive results from molecular analysis in 147 patients. J Inherit Metab Dis. 2013 Jan;36(1):7-13. doi: 10.1007/s10545-012-9485-y. Epub, 2012 Apr 25. PMID:22526846 doi:10.1007/s10545-012-9485-y
↑ Groselj U, Tansek MZ, Kovac J, Hovnik T, Podkrajsek KT, Battelino T. Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene. Mol Genet Metab. 2012 Jun;106(2):142-8. doi: 10.1016/j.ymgme.2012.03.015. Epub, 2012 Apr 1. PMID:22513348 doi:10.1016/j.ymgme.2012.03.015
↑ Bosco P, Cali F, Meli C, Mollica F, Zammarchi E, Cerone R, Vanni C, Palillo L, Greco D, Romano V. Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia. Hum Mutat. 1998;11(3):240-3. PMID:9521426 doi:<240::AID-HUMU9>3.0.CO;2-L 10.1002/(SICI)1098-1004(1998)11:3<240::AID-HUMU9>3.0.CO;2-L
↑ Yang Y, Drummond-Borg M, Garcia-Heras J. Molecular analysis of phenylketonuria (PKU) in newborns from Texas. Hum Mutat. 2001 Jun;17(6):523. PMID:11385716 doi:10.1002/humu.1141
↑ Muntau AC, Roschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA. Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N Engl J Med. 2002 Dec 26;347(26):2122-32. PMID:12501224 doi:10.1056/NEJMoa021654
↑ Economou-Petersen E, Henriksen KF, Guldberg P, Guttler F. Molecular basis for nonphenylketonuria hyperphenylalaninemia. Genomics. 1992 Sep;14(1):1-5. PMID:1358789
↑ Abadie V, Jaruzelska J, Lyonnet S, Millasseau P, Berthelon M, Rey F, Munnich A, Rey J. Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. Hum Mol Genet. 1993 Jan;2(1):31-4. PMID:8098245
↑ Guldberg P, Henriksen KF, Thony B, Blau N, Guttler F. Molecular heterogeneity of nonphenylketonuria hyperphenylalaninemia in 25 Danish patients. Genomics. 1994 May 15;21(2):453-5. PMID:8088845 doi:http://dx.doi.org/10.1006/geno.1994.1296
↑ Kibayashi M, Nagao M, Chiba S. Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia. J Hum Genet. 1998;43(4):231-6. PMID:9852673 doi:10.1007/s100380050079
↑ Chen KJ, Chao HK, Hsiao KJ, Su TS. Identification and characterization of a novel liver-specific enhancer of the human phenylalanine hydroxylase gene. Hum Genet. 2002 Mar;110(3):235-43. Epub 2002 Feb 5. PMID:11935335 doi:10.1007/s00439-002-0677-7
↑ Erlandsen H, Bjorgo E, Flatmark T, Stevens RC. Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry. 2000 Mar 7;39(9):2208-17. PMID:10694386

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1dmw"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1dmw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The January 2005 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Phenylalanine Hydroxylase''  by Shuchismita Dutta and David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2005_1 10.2210/rcsb_pdb/mom_2005_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DMW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DMW FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pah|1pah]], [[2pah|2pah]], [[3pah|3pah]], [[4pah|4pah]], [[5pah|5pah]], [[6pah|6pah]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pah|1pah]], [[2pah|2pah]], [[3pah|3pah]], [[4pah|4pah]], [[5pah|5pah]], [[6pah|6pah]]</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylalanine_4-monooxygenase Phenylalanine 4-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.16.1 1.14.16.1] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phenylalanine_4-monooxygenase Phenylalanine 4-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.16.1 1.14.16.1] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dmw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dmw RCSB], [http://www.ebi.ac.uk/pdbsum/1dmw PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dmw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dmw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dmw RCSB], [http://www.ebi.ac.uk/pdbsum/1dmw PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/PH4H_HUMAN PH4H_HUMAN]] Defects in PAH are the cause of phenylketonuria (PKU) [MIM:[http://omim.org/entry/261600 261600]]. PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.<ref>PMID:8594560</ref> <ref>PMID:2840952</ref> <ref>PMID:2564729</ref> <ref>PMID:2615649</ref> <ref>PMID:1975559</ref> <ref>PMID:1671810</ref> <ref>PMID:2014802</ref> <ref>PMID:1672294</ref> <ref>PMID:1672290</ref> <ref>PMID:1679030</ref> <ref>PMID:1709636</ref> <ref>PMID:1355066</ref> <ref>PMID:1363837</ref> <ref>PMID:1363838</ref> <ref>PMID:8406445</ref> <ref>PMID:8068076</ref> <ref>PMID:7833954</ref> <ref>PMID:8889583</ref> <ref>PMID:8889590</ref> <ref>PMID:9048935</ref> <ref>PMID:9101291</ref> <ref>PMID:9521426</ref> <ref>PMID:9600453</ref> <ref>PMID:10200057</ref> <ref>PMID:9452061</ref> <ref>PMID:9452062</ref> <ref>PMID:9792407</ref> <ref>PMID:9792411</ref> <ref>PMID:9950317</ref> <ref>PMID:10679941</ref> <ref>PMID:11326337</ref> <ref>PMID:11180595</ref> <ref>PMID:11385716</ref> <ref>PMID:11461196</ref> <ref>PMID:12501224</ref> <ref>PMID:18538294</ref> <ref>PMID:22526846</ref> <ref>PMID:22513348</ref>   Defects in PAH are the cause of non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:[http://omim.org/entry/261600 261600]]. Non-PKU HPA is a mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.  Defects in PAH are the cause of hyperphenylalaninemia (HPA) [MIM:[http://omim.org/entry/261600 261600]]. HPA is the mildest form of phenylalanine hydroxylase deficiency.<ref>PMID:9521426</ref> <ref>PMID:11385716</ref> <ref>PMID:12501224</ref> <ref>PMID:1358789</ref> <ref>PMID:8098245</ref> <ref>PMID:8088845</ref> <ref>PMID:9852673</ref> <ref>PMID:11935335</ref>
@@ Line 41: / Line 41: @@
 [[Category: Phenylalanine Hydroxylase]]
 [[Category: RCSB PDB Molecule of the Month]]
-[[Category: Erlandsen, H.]]
+[[Category: Erlandsen, H]]
-[[Category: Flatmark, T.]]
+[[Category: Flatmark, T]]
-[[Category: Stevens, R C.]]
+[[Category: Stevens, R C]]
 [[Category: 8-dihydro-l-biopterin]]
 [[Category: Cofactor]]
 [[Category: Iron enzyme]]
 [[Category: Oxidoreductase]]

1dmw

From Proteopedia

Revision as of 21:03, 22 December 2014

CRYSTAL STRUCTURE OF DOUBLE TRUNCATED HUMAN PHENYLALANINE HYDROXYLASE WITH BOUND 7,8-DIHYDRO-L-BIOPTERIN

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Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

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