Ectonucleotide pyrophosphatase/phosphodiesterase: Difference between revisions

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<StructureSection load='4gtw' size='400' side='right' caption='Mouse glycosylated Se-Met ENPP1 complex with AMP and Ca+2 (green) and Zn+2 ions (grey) (PDB code [[4gtw]])' scene='77/775922/Cv/1'>
<StructureSection load='4gtw' size='400' side='right' caption='Mouse glycosylated Se-Met ENPP1 complex with AMP and Ca+2 (green) and Zn+2 ions (grey) (PDB code [[4gtw]])' scene='77/775922/Cv/1'>


 
__TOC__
== Function ==
== Function ==


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*'''Ectonucleotide pyrophosphatase/phosphodiesterase 1''' (ENPP1) converts extracellular nucleotides into inorganic pyrophosphate<ref>PMID:23041369</ref>.  It regulates osteoblast differentiation<ref>PMID:21930712</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 1''' (ENPP1) converts extracellular nucleotides into inorganic pyrophosphate<ref>PMID:23041369</ref>.  It regulates osteoblast differentiation<ref>PMID:21930712</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 2''' or '''autotoxin''' (ENPP2) hydrolyzes lysophospholipids<ref>PMID:23041369</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 2''' or '''autotaxin''' (ENPP2) hydrolyzes lysophospholipids<ref>PMID:23041369</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 4''' or (ENPP4) is an extracellular membrane protein which hydrolyzes adenine dinucleotide Ap3A thus causing platelet aggregation<ref>PMID:24338010</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 4''' or (ENPP4) is an extracellular membrane protein which hydrolyzes adenine dinucleotide Ap3A thus causing platelet aggregation<ref>PMID:24338010</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 6''' (ENPP6) hydrolyzes choline-containing compounds like  lysophosphatidylcholine<ref>PMID:23161088</ref><br />
*'''Ectonucleotide pyrophosphatase/phosphodiesterase 6''' (ENPP6) hydrolyzes choline-containing compounds like  lysophosphatidylcholine<ref>PMID:23161088</ref><br />
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== Structural highlights ==
== Structural highlights ==


The active site of ENPP1 contains <scene name='77/775922/Cv/3'>two functionally significant Zn+2 ions</scene> and the <scene name='77/775922/Cv/4'>reaction product AMP</scene><ref>PMID:23027977</ref>.
The active site of ENPP1 contains <scene name='77/775922/Cv/5'>two functionally significant Zn+2 ions</scene> and the <scene name='77/775922/Cv/6'>reaction product AMP</scene><ref>PMID:23027977</ref>. <scene name='77/775922/Cv/7'>Surface representation of the AMP binding site</scene>.


</StructureSection>
== 3D Structures of ectonucleotide pyrophosphatase/phosphodiesterase ==
== 3D Structures of ectonucleotide pyrophosphatase/phosphodiesterase ==
[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*ENPP1
 
**[[4b56]] – mENPP1 – mouse <br />
**[[2ys0]] – hENPP1 somatomedin domain – human - NMR <br />
**[[4gtw]], [[4gtx]], [[4gty]], [[4gtz]] – mENPP1 (mutant) + nucleotide <br />
 
*ENPP2 (Autotoxin)
 
**[[5ijq]], [[5ijs]] – rENPP2 - rat<br />
**[[2xr9]] – rENPP2 (mutant) <br />
**[[5l0b]], [[5l0e]], [[5l0k]] – rENPP2 + inhibitor <br />
**[[5lqq]], [[5m0d]], [[2xrg]], [[5m0e]], [[5m0m]], [[5m0s]] – rENPP2 (mutant) + inhibitor <br />
**[[5dlt]], [[5dlw]], [[5dlv]] – rENPP2 (mutant) + steroid <br />
**[[3nkm]], [[5inh]] – mENPP2 <br />
**[[3nkn]], [[3nko]], [[3nkp]], [[3nkq]], [[3nkr]] – mENPP2 + lipid<br />
**[[5hrt]] – mENPP2 + DNA<br />
**[[3wav]], [[3waw]], [[3wax]], [[3way]], [[5lia]], [[5ohi]], [[5olb]] – mENPP2 + inhibitor<br />
**[[4zg6]], [[4zg7]], [[4zg9]], [[4zga]], [[5kxa]], [[5m7m]], [[5mhp]] – hENPP2 (mutant) + inhibitor <br />
 
*ENPP3
 
**[[6c01]] – hENPP3 <br />
**[[6c02]] – hENPP3 + AMPCPP <br />
**[[6f2t]] – rENPP3 <br />
 
*ENPP4
 
**[[4lr2]] – hENPP4 <br />
**[[4lqy]] – hENPP4 + AMP <br />
 
*ENPP5
 
**[[5vem]], [[5ven]] – hENPP5  <br />
**[[5veo]] – mENPP5 (mutant) + AMP <br />
 
*ENPP6
 
**[[5ege]] – mENPP6 (mutant) <br />
**[[5egh]] – mENPP6 (mutant) + phosphocholine<br />
 
*ENPP7 (Alkaline sphingomyelinase)


**[[5udy]] – hENPP7 <br />
**[[5tcd]] – hENPP7 + phosphocholine<br />
}}
== References ==
== References ==
<references/>
<references/>


[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 18:33, 29 December 2020


Function

Ectonucleotide pyrophosphatase/phosphodiesterase family of proteins mediates purinergic signaling by degrading extracellular nucleotides and also participate in phospholipid metabolism[1]

  • Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) converts extracellular nucleotides into inorganic pyrophosphate[2]. It regulates osteoblast differentiation[3]
  • Ectonucleotide pyrophosphatase/phosphodiesterase 2 or autotaxin (ENPP2) hydrolyzes lysophospholipids[4]
  • Ectonucleotide pyrophosphatase/phosphodiesterase 4 or (ENPP4) is an extracellular membrane protein which hydrolyzes adenine dinucleotide Ap3A thus causing platelet aggregation[5]
  • Ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) hydrolyzes choline-containing compounds like lysophosphatidylcholine[6]
  • Ectonucleotide pyrophosphatase/phosphodiesterase 7 or alkaline sphingomyelinase (ENPP7) converts sphingomyelin into ceramide and phosphocholine[7]

Relevance

ENPP7 may protect the intestinal mucosa from inflammation and tumorigenesis. ENPP3 is associated with carcinogenesis of human colon cancer[8].

Structural highlights

The active site of ENPP1 contains and the [9]. .

3D Structures of ectonucleotide pyrophosphatase/phosphodiesterase

Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures


Mouse glycosylated Se-Met ENPP1 complex with AMP and Ca+2 (green) and Zn+2 ions (grey) (PDB code 4gtw)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Gorelik A, Randriamihaja A, Illes K, Nagar B. A Key Tyrosine Substitution Restricts Nucleotide Hydrolysis by the Ectoenzyme NPP5. FEBS J. 2017 Sep 12. doi: 10.1111/febs.14266. PMID:28898552 doi:http://dx.doi.org/10.1111/febs.14266
  2. ↑ Jansen S, Perrakis A, Ulens C, Winkler C, Andries M, Joosten RP, Van Acker M, Luyten FP, Moolenaar WH, Bollen M. Structure of NPP1, an Ectonucleotide Pyrophosphatase/Phosphodiesterase Involved in Tissue Calcification. Structure. 2012 Oct 2. pii: S0969-2126(12)00330-9. doi:, 10.1016/j.str.2012.09.001. PMID:23041369 doi:http://dx.doi.org/10.1016/j.str.2012.09.001
  3. ↑ Nam HK, Liu J, Li Y, Kragor A, Hatch NE. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) protein regulates osteoblast differentiation. J Biol Chem. 2011 Nov 11;286(45):39059-71. doi: 10.1074/jbc.M111.221689. Epub, 2011 Sep 19. PMID:21930712 doi:http://dx.doi.org/10.1074/jbc.M111.221689
  4. ↑ Jansen S, Perrakis A, Ulens C, Winkler C, Andries M, Joosten RP, Van Acker M, Luyten FP, Moolenaar WH, Bollen M. Structure of NPP1, an Ectonucleotide Pyrophosphatase/Phosphodiesterase Involved in Tissue Calcification. Structure. 2012 Oct 2. pii: S0969-2126(12)00330-9. doi:, 10.1016/j.str.2012.09.001. PMID:23041369 doi:http://dx.doi.org/10.1016/j.str.2012.09.001
  5. ↑ Albright RA, Ornstein DL, Cao W, Chang WC, Robert D, Tehan M, Hoyer D, Liu L, Stabach P, Yang G, De La Cruz EM, Braddock DT. Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke. J Biol Chem. 2014 Feb 7;289(6):3294-306. doi: 10.1074/jbc.M113.505867. Epub 2013 , Dec 12. PMID:24338010 doi:http://dx.doi.org/10.1074/jbc.M113.505867
  6. ↑ Greiner-Tollersrud L, Berg T, Stensland HM, Evjen G, Greiner-Tollersrud OK. Bovine brain myelin glycerophosphocholine choline phosphodiesterase is an alkaline lysosphingomyelinase of the eNPP-family, regulated by lysosomal sorting. Neurochem Res. 2013 Feb;38(2):300-10. doi: 10.1007/s11064-012-0921-z. Epub 2012, Nov 17. PMID:23161088 doi:http://dx.doi.org/10.1007/s11064-012-0921-z
  7. ↑ Gorelik A, Liu F, Illes K, Nagar B. Crystal Structure of the Human Alkaline Sphingomyelinase Provides Insights into Substrate Recognition. J Biol Chem. 2017 Mar 14. pii: jbc.M116.769273. doi: 10.1074/jbc.M116.769273. PMID:28292932 doi:http://dx.doi.org/10.1074/jbc.M116.769273
  8. ↑ Yano Y, Hayashi Y, Sano K, Shinmaru H, Kuroda Y, Yokozaki H, Yoon S, Kasuga M. Expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterase I-3 (E-NPP3/CD203c/PD-I beta/B10/gp130RB13-6) in human colon carcinoma. Int J Mol Med. 2003 Nov;12(5):763-6. PMID:14533006
  9. ↑ Kato K, Nishimasu H, Okudaira S, Mihara E, Ishitani R, Takagi J, Aoki J, Nureki O. Crystal structure of Enpp1, an extracellular glycoprotein involved in bone mineralization and insulin signaling. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16876-81. doi:, 10.1073/pnas.1208017109. Epub 2012 Oct 1. PMID:23027977 doi:http://dx.doi.org/10.1073/pnas.1208017109

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