Editing ATPase

{{Short description|Dephosphorylation enzyme}}
{{Infobox enzyme
| Name       = Adenosinetriphosphatase
| EC_number  = 3.6.1.3
| CAS_number = 9000-83-3
| GO_code    =
| image      = 
| width      = 
| caption    =  
}}
[[Image:Adenosintriphosphat protoniert.svg|200px|thumb|[[Adenosine triphosphate]]]]
[[Image:Adenosindiphosphat protoniert.svg|200px|thumb|[[Adenosine diphosphate]]]]
[[Image:Adenosinmonophosphat_protoniert.svg|200px|thumb|[[Adenosine monophosphate]]]]
'''ATPases''' ({{EC number|3.6.1.3}}, '''A'''denosine 5'-'''T'''ri'''P'''hosphat'''ase''', adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of [[enzyme]]s that [[catalysis|catalyze]] the [[decomposition]] of [[adenosine triphosphate|ATP]] into [[adenosine diphosphate|ADP]] and a free [[phosphate|phosphate ion]]<ref>{{cite journal | vauthors = Geider K, Hoffmann-Berling H | title = Proteins controlling the helical structure of DNA | journal = Annual Review of Biochemistry | volume = 50 | pages = 233–60 | year = 1981 | pmid = 6267987 | doi = 10.1146/annurev.bi.50.070181.001313 }}</ref><ref>{{cite book | chapter = Myosin adenosine triphosphatase | title = The Enzymes | vauthors = Kielley WW |year = 1961 |volume = 5 |pages = 159–168 | veditors = Boyer PD, Lardy H, Myrbäck K |edition = 2nd |publisher = Academic Press |location = New York }}</ref><ref>{{cite journal | vauthors = Martin SS, Senior AE | title = Membrane adenosine triphosphatase activities in rat pancreas | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 602 | issue = 2 | pages = 401–18 | date = November 1980 | pmid = 6252965 | doi = 10.1016/0005-2736(80)90320-x }}</ref><ref>{{cite journal | title = Proton-linked transport in chromaffin granules | vauthors = Njus D, Knoth J, Zallakian M |journal = Current Topics in Bioenergetics |year = 1981 |volume = 11 |pages = 107–147 |doi = 10.1016/B978-0-12-152511-8.50010-4 }}</ref><ref>{{cite journal | vauthors = Riley MV, Peters MI | title = The localization of the anion-sensitive ATPase activity in corneal endothelium | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 644 | issue = 2 | pages = 251–6 | date = June 1981 | pmid = 6114746 | doi = 10.1016/0005-2736(81)90382-5 }}</ref><ref>{{cite journal | vauthors = Tjian R | title = Regulation of viral transcription and DNA replication by the SV40 large T antigen | volume = 93 | pages = 5–24 | year = 1981 | pmid = 6269805 | doi = 10.1007/978-3-642-68123-3_2 | isbn = 978-3-642-68125-7 | journal = Current Topics in Microbiology and Immunology }}</ref> or the inverse reaction. This [[dephosphorylation]] reaction releases [[energy]], which the enzyme (in most cases) harnesses to drive other [[chemical reaction]]s that would not otherwise occur. This process is widely used in all known forms of [[life]].

Some such enzymes are [[integral membrane protein]]s (anchored within [[biological membrane]]s), and move [[solutes]] across the membrane, typically against their concentration gradient. These are called transmembrane ATPases.

==Functions==
[[Image:Scheme sodium-potassium pump-en.svg|thumb|250px|[[NaKATPase|Na<sup>+</sup>/K<sup>+</sup>ATPase]] ]]
Transmembrane ATPases import metabolites necessary for [[cell (biology)|cell]] [[metabolism]] and export toxins, wastes, and solutes that can hinder cellular processes. An important example is the [[sodium-potassium pump]] (Na<sup>+</sup>/K<sup>+</sup>ATPase) that maintains the [[membrane potential|cell membrane potential]]. Another example is the [[hydrogen potassium ATPase]] (H<sup>+</sup>/K<sup>+</sup>ATPase or gastric proton pump) that acidifies the contents of the stomach. ATPase is genetically conserved in animals; therefore, [[cardenolides]] which are toxic steroids produced by plants that act on ATPases, make general and effective animal toxins that act dose dependently.<ref>{{cite journal | vauthors = Dobler S, Dalla S, Wagschal V, Agrawal AA | title = Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na,K-ATPase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 32 | pages = 13040–5 | date = August 2012 | pmid = 22826239 | pmc = 3420205 | doi = 10.1073/pnas.1202111109 | doi-access = free }}</ref>

Besides exchangers, other categories of transmembrane ATPase include [[co-transport]]ers and pumps (however, some exchangers are also pumps). Some of these, like the Na<sup>+</sup>/K<sup>+</sup>ATPase, cause a net flow of charge, but others do not. These are called electrogenic transporters and electroneutral transporters, respectively.<ref name="libretexts">{{cite web |title=3.2: Transport in Membranes |url=https://bio.libretexts.org/Bookshelves/Biochemistry/Book%3A_Biochemistry_Free_For_All_(Ahern_Rajagopal_and_Tan)/03%3A_Membranes/3.02%3A_Transport_in_Membranes |website=Biology LibreTexts |access-date=28 July 2022 |language=en |date=21 January 2017}}</ref>

==Structure==
The [[Walker motifs]] are a telltale protein sequence motif for nucleotide binding and hydrolysis.  Beyond this broad function, the Walker motifs can be found in almost all natural ATPases, with the notable exception of [[tyrosine kinase]]s.<ref name="pmid6329717">{{cite journal |vauthors=Walker JE, Saraste M, Runswick MJ, Gay NJ |title=Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold |journal=EMBO J. |volume=1 |issue=8 |pages=945–51 |year=1982 |pmid=6329717 |pmc=553140 |doi= 10.1002/j.1460-2075.1982.tb01276.x}}</ref> The Walker motifs commonly form a [[Beta sheet]]-turn-[[Alpha helix]] that is self-organized as a [[Nest (protein structural motif)]].  This is thought to be because modern ATPases evolved from small NTP-binding peptides that had to be self-organized.<ref name="Romero RomeroYang2018">{{cite journal | vauthors = Romero Romero ML, Yang F, Lin YR, Toth-Petroczy A, Berezovsky IN, Goncearenco A, Yang W, Wellner A, Kumar-Deshmukh F, Sharon M, Baker D, Varani G, Tawfik DS | display-authors = 6 | title = Simple yet functional phosphate-loop proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 51 | pages = E11943–E11950 | date = December 2018 | pmid = 30504143 | doi = 10.1073/pnas.1812400115 | pmc = 6304952 | doi-access = free }}</ref>

[[Protein design]] has been able to replicate the ATPase function (weakly) without using natural ATPase sequences or structures.  Importantly, while all natural ATPases have some beta-sheet structure, the designed "Alternative ATPase" lacks beta sheet structure, demonstrating that this life-essential function is possible with sequences and structures not found in nature.<ref name="WangHecht2020">{{cite journal | vauthors = Wang M, Hecht MH | title = A Completely De Novo ATPase from Combinatorial Protein Design | journal = Journal of the American Chemical Society | date = August 2020 | volume = 142 | issue = 36 | pages = 15230–15234 | pmid = 32833456 | doi = 10.1021/jacs.0c02954 }}</ref>

==Mechanism==
ATPase (also called F<sub>0</sub>F<sub>1</sub>-ATP Synthase) is a charge-transferring complex that catalyzes ATP to perform ATP synthesis by moving ions through the membrane.<ref name=":0" />

The coupling of ATP hydrolysis and transport is a chemical reaction in which a fixed number of solute molecules are transported for each ATP molecule hydrolyzed; for the Na<sup>+</sup>/K<sup>+</sup> exchanger, this is three Na<sup>+</sup> ions out of the cell and two K+ ions inside per ATP molecule hydrolyzed.

Transmembrane ATPases make use of ATP's chemical potential energy by performing mechanical work: they transport solutes in the opposite direction of their thermodynamically preferred direction of movement—that is, from the side of the membrane with low concentration to the side with high concentration. This process is referred to as [[active transport]].

For instance, inhibiting vesicular H<sup>+</sup>-ATPases would result in a rise in the pH within vesicles and a drop in the pH of the cytoplasm.

All of the ATPases share a common basic structure. Each rotary ATPase is composed of two major components: F<sub>0</sub>/A<sub>0</sub>/V<sub>0</sub> and F<sub>1</sub>/A<sub>1</sub>/V<sub>1</sub>. They are connected by 1-3 stalks to maintain stability, control rotation, and prevent them from rotating in the other direction. One stalk is utilized to transmit torque.<ref>{{cite journal | vauthors = Hahn A, Parey K, Bublitz M, Mills DJ, Zickermann V, Vonck J, Kühlbrandt W, Meier T | display-authors = 6 | title = Structure of a Complete ATP Synthase Dimer Reveals the Molecular Basis of Inner Mitochondrial Membrane Morphology | journal = Molecular Cell | volume = 63 | issue = 3 | pages = 445–456 | date = August 2016 | pmid = 27373333 | doi = 10.1016/j.molcel.2016.05.037 | doi-access = free | pmc = 4980432 }}</ref> The number of peripheral stalks is dependent on the type of ATPase: F-ATPases have one, A-ATPases have two, and V-ATPases have three. The F<sub>1</sub> catalytic domain is located on the N-side (negative-side) of the membrane and is involved in the synthesis and degradation of ATP and is involved in [[oxidative phosphorylation]]. The F<sub>0</sub> transmembrane domain is involved in the movement of ions across the membrane.<ref name=":0">{{cite journal | vauthors = Calisto F, Sousa FM, Sena FV, Refojo PN, Pereira MM | title = Mechanisms of Energy Transduction by Charge Translocating Membrane Proteins | journal = Chemical Reviews | volume = 121 | issue = 3 | pages = 1804–1844 | date = February 2021 | pmid = 33398986 | doi = 10.1021/acs.chemrev.0c00830 | doi-access = free }}</ref>

The bacterial [[ATP synthase|F<sub>0</sub>F<sub>1</sub>-ATPase]] consists of the soluble F<sub>1</sub> domain and the transmembrane F<sub>0</sub> domain, which is composed of several subunits with varying stoichiometry. There are two subunits, γ, and ε, that form the central stalk and they are linked to F<sub>0</sub>. F<sub>0</sub> contains a c-subunit oligomer in the shape of a ring (c-ring). The α subunit is close to the subunit b<sub>2</sub> and makes up the stalk that connects the transmembrane subunits to the α3β3 and δ subunits. F-ATP synthases are identical in appearance and function except for the mitochondrial F<sub>0</sub>F<sub>1</sub>-ATP synthase, which contains 7-9 additional subunits.<ref name=":0" />

The [[electrochemical potential]] is what causes the c-ring to rotate in a clockwise direction for ATP synthesis. This causes the central stalk and the catalytic domain to change shape. Rotating the c-ring causes three ATP molecules to be made, which then causes H<sup>+</sup> to move from the P-side (positive-side) of the membrane to the N-side (negative-side) of the membrane. The counterclockwise rotation of the c-ring is driven by ATP hydrolysis and ions move from the N-side to the P-side, which helps to build up electrochemical potential.<ref name=":0" />

==Transmembrane ATP synthases==
{{main|ATP synthase}}

The [[ATP synthase]] of [[mitochondria]] and [[chloroplast]]s is an [[Anabolism|anabolic]] enzyme that harnesses the energy of a transmembrane [[proton]] gradient as an energy source for adding an [[inorganic phosphate]] group to a molecule of [[adenosine diphosphate]] (ADP) to form a molecule of adenosine triphosphate (ATP).

This enzyme works when a proton moves down the concentration gradient, giving the enzyme a spinning motion. This unique spinning motion bonds ADP and P together to create ATP.

ATP synthase can also function in reverse, that is, use energy released by ATP hydrolysis to pump protons against their electrochemical gradient.

==Classification==
There are different types of ATPases, which can differ in function (ATP synthesis and/or hydrolysis), structure (F-, V- and A-ATPases contain rotary motors) and in the type of ions they transport.

* Rotary ATPases<ref name=pmid24878343>{{cite journal | vauthors = Stewart AG, Laming EM, Sobti M, Stock D | title = Rotary ATPases--dynamic molecular machines | journal = Current Opinion in Structural Biology | volume = 25 | pages = 40–8 | date = April 2014 | pmid = 24878343 | doi = 10.1016/j.sbi.2013.11.013 | doi-access = free }} <!-- Similar 23369889 --></ref><ref>{{cite journal | vauthors = Kühlbrandt W, Davies KM | title = Rotary ATPases: A New Twist to an Ancient Machine | journal = Trends in Biochemical Sciences | volume = 41 | issue = 1 | pages = 106–116 | date = January 2016 | pmid = 26671611 | doi = 10.1016/j.tibs.2015.10.006 }}</ref>
**[[F-ATPase]]s (F1FO-ATPases) in [[mitochondria]], [[chloroplast]]s and [[bacteria]]l [[plasma membrane]]s are the prime producers of ATP, using the proton gradient generated by [[oxidative phosphorylation]] (mitochondria) or [[photosynthesis]] (chloroplasts).<ref>{{cite journal | vauthors = Watanabe R, Noji H | title = Chemomechanical coupling mechanism of F(1)-ATPase: catalysis and torque generation | journal = FEBS Letters | volume = 587 | issue = 8 | pages = 1030–1035 | date = April 2013 | pmid = 23395605 | doi = 10.1016/j.febslet.2013.01.063 }}</ref>
*** F-ATPases lacking a [[ATP synthase delta/OSCP subunit|delta/OSCP subunit]] move sodium ions instead. They are proposed to be called [[N-ATPase]]s, since they seem to form a distinct group that is further apart from usual F-ATPases than A-ATPases are from V-ATPases.<ref>{{cite journal | vauthors = Dibrova DV, Galperin MY, Mulkidjanian AY | title = Characterization of the N-ATPase, a distinct, laterally transferred Na+-translocating form of the bacterial F-type membrane ATPase | journal = Bioinformatics | volume = 26 | issue = 12 | pages = 1473–1476 | date = June 2010 | pmid = 20472544 | pmc = 2881411 | doi = 10.1093/bioinformatics/btq234 | doi-access = free }}</ref>
**[[V-ATPase]]s (V1VO-ATPases) are primarily found in eukaryotic vacuoles, catalysing ATP hydrolysis to transport solutes and lower pH in organelles like [[proton pump]] of lysosome.
**[[A-ATPase]]s (A1AO-ATPases) are found in [[Archaea]] and some extremophilic bacteria. They are arranged like V-ATPases, but function like F-ATPases mainly as ATP synthases.
**Many homologs that are not necessarily rotaty exist. See {{section link|ATP synthase|Evolution}}.
*[[P-ATPase]]s (E1E2-ATPases) are found in bacteria, fungi and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
*'''E-ATPases''' are [[cell-surface]] [[enzyme]]s that hydrolyze a range of NTPs, including extracellular ATP. Examples include ecto-ATPases, [[CD39]]s, and ecto-ATP/Dases, all of which are members of a "[[GDA1 CD39]]" superfamily.<ref>{{cite journal | vauthors = Knowles AF | title = The GDA1_CD39 superfamily: NTPDases with diverse functions | journal = Purinergic Signalling | volume = 7 | issue = 1 | pages = 21–45 | date = March 2011 | pmid = 21484095 | pmc = 3083126 | doi = 10.1007/s11302-010-9214-7 }}</ref>
*[[AAA proteins]] are a family of ring-shaped [[P-loop]] [[Nucleoside-triphosphatase|NTPase]]s.

===P-ATPase===
{{main|P-ATPase}}
[[P-ATPase]]s (sometime known as E1-E2 ATPases) are found in bacteria and also in eukaryotic plasma membranes and organelles. Its name is due to short time attachment of inorganic phosphate at the aspartate residues at the time of activation. Function of P-ATPase is to transport a variety of different compounds, like ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transports a specific type of ion. P-ATPases may be composed of one or two polypeptides, and can usually take two main conformations, E1 and E2.

===Human genes===
* [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup> transporting]]: [[ATP1A1]], [[ATP1A2]], [[ATP1A3]], [[ATP1A4]], [[ATP1B1]], [[ATP1B2]], [[ATP1B3]], [[ATP1B4]]
* [[Calcium ATPase|Ca<sup>++</sup> transporting]]: [[ATP2A1]], [[ATP2A2]], [[ATP2A3]], [[ATP2B1]], [[ATP2B2]], [[ATP2B3]], [[ATP2B4]], [[ATP2C1]], [[ATP2C2]]
* [[Hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup> exchanging]]: [[Hydrogen potassium ATPase|ATP4A]]
* [[ATP synthase|H<sup>+</sup> transporting, mitochondrial]]: [[ATP5A1]], [[ATP5B]], [[ATP5C1]], [[ATP5C2]], [[ATP5D]], [[ATP5E]], [[ATP5F1]], [[ATP5MC1]], [[ATP5G2]], [[ATP5G3]], [[ATP5H]], [[ATP5I]], [[ATP5J]], [[ATP5J2]], [[ATP5L]], [[ATP5L2]], [[ATP5O]], [[ATP5S]], [[MT-ATP6]], [[MT-ATP8]]
* [[V-ATPase|H<sup>+</sup> transporting, lysosomal]]: [[ATP6AP1]], [[ATP6AP2]], [[ATP6V1A]], [[ATP6V1B1]], [[ATP6V1B2]], [[ATP6V1C1]], [[ATP6V1C2]], [[ATP6V1D]], [[ATP6V1E1]], [[ATP6V1E2]], [[ATP6V1F]], [[ATP6V1G1]], [[ATP6V1G2]], [[ATP6V1G3]], [[ATP6V1H]], [[ATP6V0A1]], [[ATP6V0A2]], [[ATP6V0A4]], [[ATP6V0B]], [[ATP6V0C]], [[ATP6V0D1]], [[ATP6V0D2]], [[ATP6V0E]]
* Cu<sup>++</sup> transporting: [[ATP7A]], [[ATP7B]]
* Class I, type 8: [[ATP8A1]], [[ATP8B1]], [[ATP8B2]], [[ATP8B3]], [[ATP8B4]]
* Class II, type 9: [[ATP9A]], [[ATP9B]]
* Class V, type 10: [[ATP10A]], [[ATP10B]], [[ATP10D]]
* Class VI, type 11: [[ATP11A]], [[ATP11B]], [[ATP11C]]
* H<sup>+</sup>/K<sup>+</sup> transporting, nongastric: [[ATP12A]]
* type 13: [[ATP13A1]], [[ATP13A2]], [[ATP13A3]], [[ATP13A4]], [[ATP13A5]]

== See also ==
*[[ATP synthase]]
*[[ATP synthase alpha/beta subunits]]
*[[AAA proteins]]
*[[P-ATPase]]

== References ==
{{reflist}}

== External links ==
{{Commons category}}
*[http://www.atpsynthase.info/ "ATP synthase - a splendid molecular machine"]
* {{MeshName|ATPase}}
* [http://www.pdbe.org/emsearch/atpase Electron microscopy structures of ATPases from the EM Data Bank(EMDB)]

{{Ion pumps}}
{{Acid anhydride hydrolases}}
{{Enzymes}}
{{Authority control}}
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[[Category:EC 3.6.1]]
[[Category:EC 3.6.3]]
[[Category:Integral membrane proteins]]
[[Category:Copper enzymes]]