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Updated: May 11, 2026
09:11
Screening for Thermotoga maritima Membrane-Bound Pyrophosphatase Inhibitors
Published on: November 23, 2019
Inorganic pyrophosphatases: one substrate, three mechanisms
Tommi Kajander1, Juho Kellosalo, Adrian Goldman
1Institute of Biotechnology, University of Helsinki, Helsinki, Finland. tommi.kajander@helsinki.fi
FEBS Letters
|May 21, 2013
Summary
Membrane-integral pyrophosphatases (PPases) use pyrophosphate hydrolysis to pump ions. Their novel 16-transmembrane helix structure reveals a coupling funnel linking the active site to the ion gate, suggesting pyrophosphate binding drives pumping.
Area of Science:
- Biochemistry
- Structural Biology
- Membrane Protein Research
Background:
- Soluble inorganic pyrophosphatases (PPases) hydrolyze pyrophosphate to phosphate.
- Membrane-integral PPases couple pyrophosphate hydrolysis to ion (Na+/H+) pumping, recycling energy.
- Recent structures revealed novel 16-transmembrane helix membrane proteins for H+-pumping (mung bean) and Na+-pumping (Thermotoga maritima).
Purpose of the Study:
- To elucidate the mechanism of ion pumping by membrane-integral pyrophosphatases.
- To compare the structural and functional aspects of different membrane-integral PPases.
- To understand how pyrophosphate hydrolysis is coupled to ion transport.
Main Methods:
- Comparative analysis of active sites and structural data.
- Investigation of fluoride inhibition effects.
- Evaluation of existing models for ion transport mechanisms.
Main Results:
- The H+-pumping and Na+-pumping PPases share a novel 16-transmembrane helix structure.
- A charged "coupling funnel" connects the hydrolytic active site to an ionic gate.
- The hydrolytic center is located significantly above the membrane.
- Fluoride inhibition data provides insights into the active site and transport mechanism.
Conclusions:
- Membrane-integral PPases likely utilize pyrophosphate binding to energize ion pumping.
- The unique structural features facilitate the coupling of hydrolysis to transport.
- This mechanism represents an evolutionarily ancient strategy for energy recycling.
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