1s18: Difference between revisions

Latest revision as of 08:27, 14 February 2024

Structure and protein design of human apyrase

Structural highlights

1s18 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:	ACT, CA, TRS
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CANT1_HUMAN Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

CANT1_HUMAN Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Smith TM, Hicks-Berger CA, Kim S, Kirley TL. Cloning, expression, and characterization of a soluble calcium-activated nucleotidase, a human enzyme belonging to a new family of extracellular nucleotidases. Arch Biochem Biophys. 2002 Oct 1;406(1):105-15. PMID:12234496
↑ Yang M, Kirley TL. Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change. Biochemistry. 2004 Jul 20;43(28):9185-94. PMID:15248776 doi:https://dx.doi.org/10.1021/bi049565o
↑ Nizon M, Huber C, De Leonardis F, Merrina R, Forlino A, Fradin M, Tuysuz B, Abu-Libdeh BY, Alanay Y, Albrecht B, Al-Gazali L, Basaran SY, Clayton-Smith J, Desir J, Gill H, Greally MT, Koparir E, van Maarle MC, MacKay S, Mortier G, Morton J, Sillence D, Vilain C, Young I, Zerres K, Le Merrer M, Munnich A, Le Goff C, Rossi A, Cormier-Daire V. Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis. Hum Mutat. 2012 Aug;33(8):1261-6. doi: 10.1002/humu.22104. Epub 2012 May 22. PMID:22539336 doi:https://dx.doi.org/10.1002/humu.22104

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Smith TM, Hicks-Berger CA, Kim S, Kirley TL. Cloning, expression, and characterization of a soluble calcium-activated nucleotidase, a human enzyme belonging to a new family of extracellular nucleotidases. Arch Biochem Biophys. 2002 Oct 1;406(1):105-15. PMID:12234496

[2] Yang M, Kirley TL. Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change. Biochemistry. 2004 Jul 20;43(28):9185-94. PMID:15248776 doi:https://dx.doi.org/10.1021/bi049565o

[3] Nizon M, Huber C, De Leonardis F, Merrina R, Forlino A, Fradin M, Tuysuz B, Abu-Libdeh BY, Alanay Y, Albrecht B, Al-Gazali L, Basaran SY, Clayton-Smith J, Desir J, Gill H, Greally MT, Koparir E, van Maarle MC, MacKay S, Mortier G, Morton J, Sillence D, Vilain C, Young I, Zerres K, Le Merrer M, Munnich A, Le Goff C, Rossi A, Cormier-Daire V. Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis. Hum Mutat. 2012 Aug;33(8):1261-6. doi: 10.1002/humu.22104. Epub 2012 May 22. PMID:22539336 doi:https://dx.doi.org/10.1002/humu.22104

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-[[Image:1s18.gif|left|200px]]<br />
-<applet load="1s18" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1s18, resolution 1.70&Aring;" />
-'''Structure and protein design of human apyrase'''<br />
-==Overview==
+==Structure and protein design of human apyrase==
-Hematophagous arthropods secrete a salivary apyrase that inhibits platelet, activation by catabolizing ADP released from damaged tissues and blood, cells. We report the X-ray crystal structures of a human enzyme of the, soluble apyrase family in its apo state and bound to a substrate analog., The structures reveal a nucleotide binding domain comprising a five-blade, beta propeller, binding determinants of the substrate and the active site, and an unusual calcium binding site with a potential regulatory function., Using a comparative structural biology approach, we were able to redesign, the human apyrase so as to enhance its ADPase activity by more than, 100-fold. The engineered enzyme is a potent inhibitor of platelet, aggregation and may serve as the basis for the development of a new class, of antithrombotic agents.
+<StructureSection load='1s18' size='340' side='right'caption='[[1s18]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[1s18]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S18 FirstGlance]. <br>
-S18 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, ACT and TRS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Apyrase Apyrase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.5 3.6.1.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S18 OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s18 OCA], [https://pdbe.org/1s18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s18 RCSB], [https://www.ebi.ac.uk/pdbsum/1s18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s18 ProSAT]</span></td></tr>
-Structure and protein design of a human platelet function inhibitor., Dai J, Liu J, Deng Y, Smith TM, Lu M, Cell. 2004 Mar 5;116(5):649-59. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15006348 15006348]
+</table>
-[[Category: Apyrase]]
+== Disease ==
+[https://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN] Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN] Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.<ref>PMID:12234496</ref> <ref>PMID:15248776</ref> <ref>PMID:22539336</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s1/1s18_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1s18 ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Dai, J.]]
+[[Category: Dai J]]
-[[Category: Deng, Y.]]
+[[Category: Deng Y]]
-[[Category: Liu, J.]]
+[[Category: Liu J]]
-[[Category: Lu, M.]]
+[[Category: Lu M]]
-[[Category: Smith, T.M.]]
+[[Category: Smith TM]]
-[[Category: ACT]]
-[[Category: CA]]
-[[Category: TRS]]
-[[Category: adpase]]
-[[Category: calcium-binding protein]]
-[[Category: five-blade beta propeller]]
-[[Category: nucleotide-binding motif]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:09:07 2007''

1s18: Difference between revisions

Latest revision as of 08:27, 14 February 2024

Structure and protein design of human apyrase

Structural highlights

Disease

Function

Evolutionary Conservation

References

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