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Measuring In Vitro ATPase Activity for Enzymatic Characterization
Published on: August 23, 2016
The ATP-grasp enzymes
Maria V Fawaz1, Melissa E Topper, Steven M Firestine
1Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, United States.
Bioorganic Chemistry
|September 17, 2011
Summary
The ATP-grasp enzymes, crucial for various metabolic pathways, feature a unique ATP-binding fold. Inhibitors targeting these enzymes show potential as antibacterial and anti-obesity agents.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- ATP-grasp enzymes are a superfamily of 21 proteins characterized by an atypical ATP-binding site, known as the ATP-grasp fold.
- This fold consists of two α+β domains that bind ATP and typically exhibit three conserved focal domains.
- Founding members include biotin carboxylase, d-ala-d-ala ligase, and glutathione synthetase, all involved in ATP-assisted reactions forming an acylphosphate intermediate.
Purpose of the Study:
- To review the structure, function, mechanism, and inhibition of the ATP-grasp enzyme superfamily.
- To highlight the significance of these enzymes in various metabolic pathways.
- To discuss the therapeutic potential of ATP-grasp enzyme inhibitors.
Main Methods:
- Literature review of existing research on ATP-grasp enzymes.
- Analysis of structural and mechanistic data.
- Examination of studies on enzyme inhibition and therapeutic applications.
Main Results:
- Most ATP-grasp enzymes catalyze ATP-assisted reactions via an acylphosphate intermediate, though some function as kinases.
- These enzymes are integral to critical metabolic pathways such as purine biosynthesis, gluconeogenesis, and fatty acid synthesis.
- Inhibitors targeting ATP-grasp enzymes are being developed for antibacterial and anti-obesity applications.
Conclusions:
- The ATP-grasp enzyme superfamily possesses a conserved structural fold crucial for its diverse functions.
- Understanding the mechanism and structure of these enzymes facilitates the development of targeted inhibitors.
- ATP-grasp enzyme inhibitors represent a promising avenue for novel therapeutic strategies.
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