Target Information

Target General Infomation
Target ID
T20514
Former ID
TTDS00342
Target Name
Delta-aminolevulinic acid dehydratase
Gene Name
ALAD
Synonyms
ALADH; Delta-aminolevulinate dehydratase; Porphobilinogen synthase; ALAD
Target Type
Successful
Disease Photodynamic therapy [ICD9: 706.1; ICD10: L70.0]
Function
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.
BioChemical Class
Carbon-oxygen lyases
UniProt ID
P13716
EC Number
EC 4.2.1.24
Sequence
MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD
VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE
ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR
DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV
LEAMTAFRRAGADIIITYYTPQLLQWLKEE
Drugs and Mode of Action
Drug(s) Aminolevulinic acid Drug Info Approved Photodynamic therapy [468013], [536361]
Porphobilinogen Drug Info Phase 2 Discovery agent [521946]
Inhibitor 3-(2-Aminoethyl)-4-(Aminomethyl)Heptanedioic Acid Drug Info [551393]
4,7-Dioxosebacic Acid Drug Info [551393]
4-Oxosebacic Acid Drug Info [551393]
5-Fluorolevulinic Acid Drug Info [551393]
5-hydroxyvaleric acid Drug Info [551381]
Aminolevulinic acid Drug Info [534911], [535413], [535718]
Beta-Mercaptoethanol Drug Info [551393]
Delta-Amino Valeric Acid Drug Info [551393]
Formic Acid Drug Info [551393]
Laevulinic Acid Drug Info [551393]
Levulinic Acid Drug Info [551393]
Porphobilinogen Drug Info [551393]
S,S-(2-Hydroxyethyl)Thiocysteine Drug Info [551393]
Pathways
BioCyc Pathway Heme biosynthesis
Tetrapyrrole biosynthesis
KEGG Pathway Porphyrin and chlorophyll metabolism
Metabolic pathways
PANTHER Pathway Heme biosynthesis
PathWhiz Pathway Porphyrin Metabolism
WikiPathways Heme Biosynthesis
Metabolism of porphyrins
References
Ref 468013(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4784).
Ref 521946ClinicalTrials.gov (NCT00418795) Porphozym in the Treatment of Acute Attacks in AIP. U.S. National Institutes of Health.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 534911A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity. Br J Haematol. 1999 Sep;106(4):931-7.
Ref 535413Melatonin protects against delta-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands. Int J Biochem Cell Biol. 2002 May;34(5):544-53.
Ref 535718Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31.
Ref 551381Structure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid. Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1222-6. Epub 2005 Aug 16.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

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