acetyl-CoA acetyltransferase 1 | Lanosterol biosynthesis pathway | IUPHAR/BPS Guide to PHARMACOLOGY

acetyl-CoA acetyltransferase 1

Target id: 2435

Nomenclature: acetyl-CoA acetyltransferase 1

Family: Lanosterol biosynthesis pathway

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for acetyl-CoA acetyltransferase 1 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 427 11q22.3 ACAT1 acetyl-CoA acetyltransferase 1
Mouse - 424 9 C-D Acat1 acetyl-Coenzyme A acetyltransferase 1
Rat - 424 8q24.1 Acat1 acetyl-CoA acetyltransferase 1
Previous and Unofficial Names
ACAT | acetoacetyl-CoA thiolase | acetyl-Co A acetyltransferase 1 mitochondrial | acetoacetyl coenzyme A thiolase
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function
PDB Id:  2IBY
Resolution:  1.85Å
Species:  Human
References:  5
Enzyme Reaction
EC Number: 2.3.1.9 2acetyl CoA = acetoacetyl CoA + coenzyme A
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
acetyl CoA Hs Km 5.08x10-4 M pKm 3.3 5
acetoacetyl CoA Hs Km 4x10-6 M pKm 5.4 Assayed in the presence of 60µM CoA 5
coenzyme A Hs Km 2x10-5 M pKm 4.7 Assayed in the presence of 10 µM acetoacetyl-CoA 5

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 16 [PMID: 16242323] Rn Inhibition 8.3 pIC50 1
pIC50 8.3 (IC50 5.4x10-9 M) [1]
compound 15b [PMID: 16242323] Rn Inhibition 8.1 pIC50 1
pIC50 8.1 (IC50 8.3x10-9 M) [1]
SM-32504 Rn Inhibition 8.0 pIC50 1
pIC50 8.0 (IC50 1.1x10-8 M) [1]
compound 15a [PMID: 16242323] Rn Inhibition 7.8 pIC50 1
pIC50 7.8 (IC50 1.4x10-8 M) [1]
SMP-797 Rn Inhibition 7.7 pIC50 1
pIC50 7.7 (IC50 2.1x10-8 M) [1]
compound 22d [PMID: 16242323] Rn Inhibition 7.4 pIC50 1
pIC50 7.4 (IC50 4.3x10-8 M) [1]
compound 22c [PMID: 16242323] Rn Inhibition 7.2 pIC50 1
pIC50 7.2 (IC50 6.1x10-8 M) [1]
compound 18a [PMID: 16242323] Rn Inhibition 6.4 pIC50 1
pIC50 6.4 (IC50 3.82x10-7 M) [1]
compound 26b [PMID: 16242323] Rn Inhibition 6.4 pIC50 1
pIC50 6.4 (IC50 4.27x10-7 M) [1]
compound 26a [PMID: 16242323] Rn Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 4.52x10-7 M) [1]
compound 26c [PMID: 16242323] Rn Inhibition 6.3 pIC50 1
pIC50 6.3 (IC50 5.4x10-7 M) [1]
compound 18b [PMID: 16242323] Rn Inhibition 6.2 pIC50 1
pIC50 6.2 (IC50 6.8x10-7 M) [1]
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alpha-methylacetoacetic aciduria
Synonyms: Beta-ketothiolase deficiency [Orphanet: ORPHA134] [Disease Ontology: DOID:14723]
Disease Ontology: DOID:14723
OMIM: 203750
Orphanet: ORPHA134
References:  2-4,6
Disease:  Psychomotor delay
References:  7
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human M389I G>A A rare missense mutation resulting from a G to A nucleotide change leads to a Met to Ile amino acid substitution 7

References

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1. Ban H, Muraoka M, Ioriya K, Ohashi N. (2006) Synthesis and biological activity of novel 4-phenyl-1,8-naphthyridin-2(1H)-on-3-yl ureas: potent acyl-CoA:cholesterol acyltransferase inhibitor with improved aqueous solubility. Bioorg. Med. Chem. Lett., 16 (1): 44-8. [PMID:16242323]

2. Fukao T, Nakamura H, Song XQ, Nakamura K, Orii KE, Kohno Y, Kano M, Yamaguchi S, Hashimoto T, Orii T et al.. (1998) Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency. Hum. Mutat., 12 (4): 245-54. [PMID:9744475]

3. Fukao T, Yamaguchi S, Orii T, Schutgens RB, Osumi T, Hashimoto T. (1992) Identification of three mutant alleles of the gene for mitochondrial acetoacetyl-coenzyme A thiolase. A complete analysis of two generations of a family with 3-ketothiolase deficiency. J. Clin. Invest., 89 (2): 474-9. [PMID:1346617]

4. Fukao T, Yamaguchi S, Tomatsu S, Orii T, Frauendienst-Egger G, Schrod L, Osumi T, Hashimoto T. (1991) Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency. Biochem. Biophys. Res. Commun., 179 (1): 124-9. [PMID:1715688]

5. Haapalainen AM, Meriläinen G, Pirilä PL, Kondo N, Fukao T, Wierenga RK. (2007) Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. Biochemistry, 46 (14): 4305-21. [PMID:17371050]

6. Wakazono A, Fukao T, Yamaguchi S, Hori T, Orii T, Lambert M, Mitchell GA, Lee GW, Hashimoto T. (1995) Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients. Hum. Mutat., 5 (1): 34-42. [PMID:7728148]

7. Wang X, Wang H, Cao M, Li Z, Chen X, Patenia C, Gore A, Abboud EB, Al-Rajhi AA, Lewis RA et al.. (2011) Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis. Hum. Mutat., 32 (12): 1450-9. [PMID:21901789]

Contributors

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How to cite this page

Helen E. Benson.
Lanosterol biosynthesis pathway: acetyl-CoA acetyltransferase 1. Last modified on 29/05/2015. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2435.