Target Information
Target General Information | Top | |||||
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Target ID |
T20514
(Former ID: TTDS00342)
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Target Name |
Delta-aminolevulinic acid dehydratase (ALAD)
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Synonyms |
Porphobilinogen synthase; Delta-aminolevulinate dehydratase; ALADH; ALAD
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Gene Name |
ALAD
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Acne vulgaris [ICD-11: ED80] | |||||
2 | Epidermal dysplasias [ICD-11: EK90] | |||||
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.
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BioChemical Class |
Alpha-carbonic anhydrase
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UniProt ID | ||||||
EC Number |
EC 4.2.1.24
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Sequence |
MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV LEAMTAFRRAGADIIITYYTPQLLQWLKEE Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A03510 | |||||
HIT2.0 ID | T63EKR |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Aminolevulinic acid hci | Drug Info | Approved | Acne vulgaris | [2], [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 12 Inhibitor drugs | + | ||||
1 | Aminolevulinic acid hci | Drug Info | [1], [4], [5] | |||
2 | Porphobilinogen | Drug Info | [6] | |||
3 | 2-Sulfhydryl-Ethanol | Drug Info | [6] | |||
4 | 3-(2-Aminoethyl)-4-(Aminomethyl)Heptanedioic Acid | Drug Info | [6] | |||
5 | 4,7-Dioxosebacic Acid | Drug Info | [6] | |||
6 | 4-Oxosebacic Acid | Drug Info | [6] | |||
7 | 5-Fluorolevulinic Acid | Drug Info | [6] | |||
8 | 5-hydroxyvaleric acid | Drug Info | [7] | |||
9 | Delta-Amino Valeric Acid | Drug Info | [6] | |||
10 | Formic Acid | Drug Info | [6] | |||
11 | Laevulinic Acid | Drug Info | [6] | |||
12 | S,S-(2-Hydroxyethyl)Thiocysteine | Drug Info | [6] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 2 BioCyc Pathways | + | ||||
1 | Heme biosynthesis | |||||
2 | Tetrapyrrole biosynthesis | |||||
KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
1 | Porphyrin and chlorophyll metabolism | |||||
2 | Metabolic pathways | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Heme biosynthesis | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Porphyrin Metabolism | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Heme Biosynthesis | |||||
2 | Metabolism of porphyrins |
References | Top | |||||
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REF 1 | Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. | |||||
REF 2 | URL: 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 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 4 | Melatonin 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 5 | A 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 6 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 7 | Structure 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. |
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