<p>ATPases (or ATP synthases) are membrane-bound enzyme complexes/ion transporters that combine ATP synthesis and/or hydrolysis with the transport of protons across a membrane. ATPases can harness the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. Some ATPases work in reverse, using the energy from the hydrolysis of ATP to create a proton gradient. There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [<cite idref="PUB00020603"/>, <cite idref="PUB00020604"/>]. The different types include:</p><p> <ul><li>F-ATPases (F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).</li><li>V-ATPases (V1V0-ATPases), which are primarily found in eukaryotic vacuoles and catalyse ATP hydrolysis to transport solutes and lower pH in organelles.</li><li>A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases (though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases).</li><li>P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.</li><li>E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.</li> </ul> </p><p>P-ATPases (sometime known as E1-E2 ATPases) (<db_xref db="EC" dbkey="3.6.3.-"/>) are found in bacteria and in a number of eukaryotic plasma membranes and organelles [<cite idref="PUB00009616"/>]. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, each of which transports a specific type of ion: H⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Ag⁺ and Ag²⁺, Zn²⁺, Co²⁺, Pb²⁺, Ni²⁺, Cd²⁺, Cu⁺ and Cu²⁺. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.</p><p>Proteins that transport heavy metals in micro-organisms and mammals share similarities in their sequences and structures. Some of these proteins are involved in bacterial resistance to toxic metals, such as lead and cadmium, while others are involved in inherited human syndromes, such as Wilson and Menkes diseases [<cite idref="PUB00005528"/>]. A conserved 30-residue domain has been found in a number of these heavy metal transport or detoxification proteins. The domain, which has been termed Heavy-Metal-Associated (HMA), contains two conserved cysteines that are probably involved in metal binding. The HMA domain has been identified in the N-terminal regions of a variety of cation-transporting ATPases (E1-E2 ATPases). </p> <p> The structure of the mercuric ion-binding protein MerP from <taxon tax_id="623">Shigella flexneri</taxon> has been determined. The fold has been classed as a ferredoxin-like alpha-beta sandwich, having a beta-alpha beta-beta alpha-beta architecture, with the two alpha-helices overlaying a four-stranded anti-parallel beta-sheet [<cite idref="PUB00000447"/>]. Structural differences between the reduced and mercury-bound forms of merP are localised to the metal-binding loop containing the consensus sequence GMTCXXC, the two cysteines of which are involved in bi-coordination of Hg(2+) [<cite idref="PUB00000447"/>].</p><p>Cadmium-transporting ATPase is an integral membrane protein present only in prokaryotes that contains a single copy of the HMA domain and is predicted to contain 4 transmembrane (TM) domains. The protein, which functions as an electroneutral antiporter, ejecting one Cd²⁺ and accumulating two protons via an energy-dependent efflux mechanism, catalyses the reaction:</p><reaction>ATP + H₂O = ADP + orthophosphate</reaction><p>More information about this protein can be found at Protein of the Month: ATP Synthases [<cite idref="PUB00020719"/>].</p> ATPase, P-type, cadmium-transporting