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N-acetyltransferase 8 like

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Target not currently curated in GtoImmuPdb

Target id: 3144

Nomenclature: N-acetyltransferase 8 like

Family: 2.3.1.- Acyltransferases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 302 4p16.3 NAT8L N-acetyltransferase 8 like
Mouse 1 299 5 B2 Nat8l N-acetyltransferase 8-like
Rat 1 299 14q21 Nat8l N-acetyltransferase 8-like
Previous and Unofficial Names Click here for help
CML3 | aspartate N-acetyltransferase | ANAT
Database Links Click here for help
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.3.1.17 Acetyl-CoA + L-aspartate <=> CoA + N-acetyl-L-aspartate (NAA)

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 5 [Stecula et al., 2020] Small molecule or natural product Hs Inhibition 6.4 pKi 3
pKi 6.4 (Ki 4x10-7 M) [3]
Physiological Consequences of Altering Gene Expression Click here for help
Knockout of the nat8l gene eliminates the brain defects that are the hallmark of human Canavan disease (ASPA deficiency).
Species:  Mouse
Tissue:  Brain
Technique:  Constitutive gene-knockout
References:  1-2
Gene Expression and Pathophysiology Comments
This enzyme is being examined as a potential druggable target for patients with Canavan disease, which is a rare neurodegenerative demyelinating disease that is caused by inherited loss-of-function mutation of aspartoacylase (ASPA; aminoacylase 2). ASPA defiiciency leads to accumulation of the critical brain metabolite N-acetyl-L-aspartate (NAA) and this is primarily responsible for the neurodegenerative symptoms of Canavan disease. Inhibitors of the N-acetyltransferase activity of NAT8L are predicterd to offer clinical utility by reversing the effect of ASPA deficiency by converting the abnormal load of NAA to L-aparagine in Canavan disease patients [3].

References

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1. Guo F, Bannerman P, Mills Ko E, Miers L, Xu J, Burns T, Li S, Freeman E, McDonough JA, Pleasure D. (2015) Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model. Ann. Neurol., 77 (5): 884-8. [PMID:25712859]

2. Sohn J, Bannerman P, Guo F, Burns T, Miers L, Croteau C, Singhal NK, McDonough JA, Pleasure D. (2017) Suppressing N-Acetyl-l-Aspartate Synthesis Prevents Loss of Neurons in a Murine Model of Canavan Leukodystrophy. J. Neurosci., 37 (2): 413-421. [PMID:28077719]

3. Stecula A, Hussain MS, Viola RE. (2020) Discovery of Novel Inhibitors of a Critical Brain Enzyme Using a Homology Model and a Deep Convolutional Neural Network. Journal of Medicinal Chemistry, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.0c00473

How to cite this page

2.3.1.- Acyltransferases: N-acetyltransferase 8 like. Last modified on 03/08/2020. Accessed on 21/10/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3144.