AI Article Synopsis
- Diacylglycerol lipase α is crucial for producing 2-arachidonoylglycerol, a major endocannabinoid in the brain.
- The study identified a catalytic triad (serine 472, aspartate 524, histidine 650) necessary for its activity, and showed that a shorter form of the enzyme can still function effectively.
- New fluorogenic and chromogenic substrates were developed, which help in assessing the inhibitory effects of compounds on diacylglycerol lipase α, proving useful for drug discovery efforts.
Article Abstract
Diacylglycerol lipase α is the key enzyme in the formation of the most prevalent endocannabinoid, 2-arachidonoylglycerol in the brain. In this study we identified the catalytic triad of diacylglycerol lipase α, consisting of serine 472, aspartate 524 and histidine 650. A truncated version of diacylglycerol lipase α, spanning residues 1-687 retains complete catalytic activity suggesting that the C-terminal domain is not required for catalysis. We also report the discovery and the characterization of fluorogenic and chromogenic substrates for diacylglycerol lipase α. Assays performed with these substrates demonstrate equipotent inhibition of diacylglycerol lipase α by tetrahydrolipastatin and RHC-20867 as compared to reactions performed with the native diacylglycerol substrate. Thus, confirming the utility of assays using these substrates for identification and kinetic characterization of inhibitors from pharmaceutical collections.
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| http://dx.doi.org/10.1016/j.bbrc.2011.07.037 | DOI Listing |
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