Targeting AWAT1 for The Prevention and Treatment of Obesity and Related Diseases

Target Name: AWAT1

NCBI ID: G158833

AWAT1

Targeting AWAT1 for The Prevention and Treatment of Obesity and Related Diseases

Long-chain-alcohol O-fatty-acyltransferase 1 (AWAT1) is a gene that encodes a protein involved in the metabolism of fatty acids, which is crucial for various cellular processes, including brain development and function, and the regulation of inflammation. Mutations in the AWAT1 gene have been linked to a range of human diseases, including obesity, type 2 diabetes, and fatty liver diseases. As a result, targeting AWAT1 has potential as a new drug target or biomarker for the prevention and treatment of these diseases.

AWAT1 function and regulation

The AWAT1 gene encodes a protein that belongs to the superfamily of alcohol-oxidizing cytoskeletal proteins (AOCPs), which are involved in the transfer of fatty acids to intracellular proteins such as ubiquitin, thereby modifying the cellular metabolism and contributing to various cellular processes. AWAT1 is a 14-kDa protein that consists of a catalytic domain and a cytoplasmic tail.

The catalytic domain of AWAT1 contains a unique alcohol-oxidizing activity, which is critical for its function in fatty acid metabolism. The catalytic domain of AWAT1 consists of a single catalytic active site and a variable number of hydrogen-bonded alcohol oxygenyl groups (OOHs) , which are involved in the transfer of fatty acids to other proteins. The oxygenyl groups in the catalytic domain can react with proteins such as ubiquitin, forming a covalent complex, which can then transfer the fatty acids to the target proteins.

The cytoplasmic tail of AWAT1 contains several important functional regions, including a region that can interact with the protein p189, another AOCP involved in fatty acid metabolism, and a region that can interact with the protein pdh1, which is involved in the production of reactive oxygen species (ROS) and contributes to the development of oxidative stress.

Mutations in AWAT1 and related genes

Mutations in the AWAT1 gene have been linked to a range of human diseases, including obesity, type 2 diabetes, and fatty liver diseases. The most well-studied mutation is the missense mutation, which results in the substitution of the amino acid Asp for Asn at position 129. This mutation has been shown to have a significant impact on the functionality of AWAT1, leading to decreased catalytic activity and increased sensitivity to high-fat meals.

Other mutations, such as the double mutation and a frameshift/insertion, have also been shown to have a significant impact on the functionality of AWAT1. The double mutation, which results in the substitution of the amino acids Asp for Asn and Glu for Lys, has been shown to have a significant impact on the stability and catalytic activity of AWAT1. The frameshift/insertion mutation, which results in the substitution of a amino acid for another, has been shown to have a significant impact on the localization and stability of AWAT1..

Targeting AWAT1 as a drug target or biomarker

The discovery of AWAT1 as a potential drug target or biomarker has significant implications for the prevention and treatment of various diseases, including obesity, type 2 diabetes, and fatty liver diseases. By targeting AWAT1, researchers may be able to develop new treatments that specifically target this protein and have a reduced risk of unintended side effects.

One approach to targeting AWAT1 is to develop small molecules that specifically interact with the catalytic active site of AWAT1. Small molecules that can bind specifically to the oxygenyl groups in the catalytic domain of AWAT1, such as 1,2-diamino-4,5- methylenedioxybenzene (DMB), have been shown to have potential as a lead compound for the development of drugs that target AWAT1. Similarly, small molecules that can specifically bind to the cytoplasmic tail of AWAT1, such as N-acetyl-L-tryptophan (NALP ), have also been shown to have potential as a lead compound for the development of drugs that target AWAT1.

Another approach to

Protein Name: Acyl-CoA Wax Alcohol Acyltransferase 1

Functions: Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters (PubMed:15671038). Shows a strong preference for decyl alcohol (C10), with less activity towards C16 and C18 alcohols (PubMed:15671038). Shows a strong preference for saturated acyl-CoAs (PubMed:15671038)

The "AWAT1 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about AWAT1 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

More Common Targets