1e51: Difference between revisions
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{{STRUCTURE_1e51| PDB=1e51 | SCENE= }} | {{STRUCTURE_1e51| PDB=1e51 | SCENE= }} | ||
=== | ===Crystal structure of native human erythrocyte 5-aminolaevulinic acid dehydratase=== | ||
==Disease== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/HEM2_HUMAN HEM2_HUMAN]] Defects in ALAD are the cause of acute hepatic porphyria (AHEPP) [MIM:[http://omim.org/entry/612740 612740]]. A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralysis, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.<ref>PMID:1569184</ref><ref>PMID:2063868</ref><ref>PMID:1309003</ref><ref>PMID:10706561</ref><ref>PMID:17236137</ref> | [[http://www.uniprot.org/uniprot/HEM2_HUMAN HEM2_HUMAN]] Defects in ALAD are the cause of acute hepatic porphyria (AHEPP) [MIM:[http://omim.org/entry/612740 612740]]. A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralysis, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.<ref>PMID:1569184</ref> <ref>PMID:2063868</ref> <ref>PMID:1309003</ref> <ref>PMID:10706561</ref> <ref>PMID:17236137</ref> | ||
==Function== | ==Function== | ||
[[http://www.uniprot.org/uniprot/HEM2_HUMAN HEM2_HUMAN]] Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.<ref>PMID:11032836</ref><ref>PMID:19812033</ref> | [[http://www.uniprot.org/uniprot/HEM2_HUMAN HEM2_HUMAN]] Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.<ref>PMID:11032836</ref> <ref>PMID:19812033</ref> | ||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID: | <ref group="xtra">PMID:012794073</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Porphobilinogen synthase]] | [[Category: Porphobilinogen synthase]] | ||
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[[Category: Dehydratase]] | [[Category: Dehydratase]] | ||
[[Category: Lead poisoning]] | [[Category: Lead poisoning]] | ||
[[Category: Lyase]] | |||
[[Category: Porphobilinogen synthase]] | [[Category: Porphobilinogen synthase]] | ||
[[Category: Tetrapyrrole biosynthesis]] | [[Category: Tetrapyrrole biosynthesis]] | ||
[[Category: Tim barrel]] | [[Category: Tim barrel]] | ||
Revision as of 12:31, 5 February 2014
Crystal structure of native human erythrocyte 5-aminolaevulinic acid dehydrataseCrystal structure of native human erythrocyte 5-aminolaevulinic acid dehydratase
DiseaseDisease
[HEM2_HUMAN] Defects in ALAD are the cause of acute hepatic porphyria (AHEPP) [MIM:612740]. A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralysis, and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.[1] [2] [3] [4] [5]
FunctionFunction
[HEM2_HUMAN] Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.[6] [7]
About this StructureAbout this Structure
1e51 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See AlsoSee Also
ReferenceReference
- ↑ Kundrat L, Martins J, Stith L, Dunbrack RL Jr, Jaffe EK. A structural basis for half-of-the-sites metal binding revealed in Drosophila melanogaster porphobilinogen synthase. J Biol Chem. 2003 Aug 15;278(33):31325-30. Epub 2003 Jun 6. PMID:12794073 doi:http://dx.doi.org/10.1074/jbc.M304124200
- ↑ Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A, Sassa S. Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria. J Clin Invest. 1992 May;89(5):1431-7. PMID:1569184 doi:http://dx.doi.org/10.1172/JCI115732
- ↑ Plewinska M, Thunell S, Holmberg L, Wetmur JG, Desnick RJ. delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote. Am J Hum Genet. 1991 Jul;49(1):167-74. PMID:2063868
- ↑ Sassa S, Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A. Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease. Trans Assoc Am Physicians. 1992;105:250-9. PMID:1309003
- ↑ Akagi R, Shimizu R, Furuyama K, Doss MO, Sassa S. Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria. Hepatology. 2000 Mar;31(3):704-8. PMID:10706561 doi:S0270913900700632
- ↑ Jaffe EK, Stith L. ALAD porphyria is a conformational disease. Am J Hum Genet. 2007 Feb;80(2):329-37. Epub 2006 Dec 21. PMID:17236137 doi:10.1086/511444
- ↑ Jaffe EK, Martins J, Li J, Kervinen J, Dunbrack RL Jr. The molecular mechanism of lead inhibition of human porphobilinogen synthase. J Biol Chem. 2001 Jan 12;276(2):1531-7. PMID:11032836 doi:10.1074/jbc.M007663200
- ↑ Lawrence SH, Ramirez UD, Selwood T, Stith L, Jaffe EK. Allosteric inhibition of human porphobilinogen synthase. J Biol Chem. 2009 Dec 18;284(51):35807-17. doi: 10.1074/jbc.M109.026294. Epub . PMID:19812033 doi:10.1074/jbc.M109.026294