Membrane bound O-acyltransferases and their inhibitors
Naoko Masumoto1, Thomas Lanyon-Hogg1, Ursula R Rodgers2
1*Department of Chemistry, Imperial College London, South Kensington Campus, London, SW7 2AZ, U.K.
Biochemical Society Transactions
|April 8, 2015
Summary
The membrane-bound O-acyltransferase (MBOATs) protein family includes PORCN, HHAT, and GOAT, which acylate proteins. This review compares their topology, assays, and small molecule inhibitors.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- The membrane-bound O-acyltransferase (MBOATs) protein family was identified in the early 2000s.
- Three key members, porcupine (PORCN), hedgehog acyltransferase (HHAT), and ghrelin O-acyltransferase (GOAT), are known to acylate specific proteins or peptides.
- Acylation by MBOATs plays crucial roles in various biological processes.
Purpose of the Study:
- To provide a comparative review of PORCN, HHAT, and GOAT.
- To discuss the determination of their membrane topology.
- To highlight the development of assays for measuring their enzymatic activities and the discovery of small molecule inhibitors.
Main Methods:
- Literature review and comparative analysis of existing studies.
- Discussion of experimental approaches for topology determination.
- Overview of assay development for enzymatic activity measurement.
- Summary of strategies for small molecule inhibitor discovery.
Main Results:
- Comparison of topological models for PORCN, HHAT, and GOAT.
- Evaluation of different assay methodologies for assessing MBOATs activity.
- Identification of key small molecule inhibitors targeting these enzymes.
- Insights into the structure-activity relationships of inhibitors.
Conclusions:
- PORCN, HHAT, and GOAT share functional similarities but exhibit distinct characteristics.
- Advancements in assay development and inhibitor discovery are crucial for understanding MBOATs functions.
- Further research into MBOATs holds potential for therapeutic interventions.
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