1s1d: Difference between revisions

Latest revision as of 06:11, 23 August 2023

Structure and protein design of human apyrase

Structural highlights

1s1d 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 1.6Å
Ligands:	ACT, CA, GP2, SO4, 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.

Publication Abstract from PubMed

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.

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:15006348^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Dai J, Liu J, Deng Y, Smith TM, Lu M. Structure and protein design of a human platelet function inhibitor. Cell. 2004 Mar 5;116(5):649-59. PMID:15006348

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

[4] Dai J, Liu J, Deng Y, Smith TM, Lu M. Structure and protein design of a human platelet function inhibitor. Cell. 2004 Mar 5;116(5):649-59. PMID:15006348

[1]

[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='1s1d' size='340' side='right'caption='[[1s1d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1s1d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S1D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1S1D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1s1d]] 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=1S1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S1D FirstGlance]. <br>
-</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=GP2:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANOSYL+ESTER'>GP2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1s18|1s18]]</div></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=GP2:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANOSYL+ESTER'>GP2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHAPY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1d OCA], [https://pdbe.org/1s1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s1d RCSB], [https://www.ebi.ac.uk/pdbsum/1s1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s1d ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1s1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1d OCA], [http://pdbe.org/1s1d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1s1d RCSB], [http://www.ebi.ac.uk/pdbsum/1s1d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1s1d ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN]] Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+[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 ==
-[[http://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>
+[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]]
@@ Line 37: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Apyrase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[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: Adpase]]
-[[Category: Calcium-binding protein]]
-[[Category: Five-blade beta propeller]]
-[[Category: Hydrolase]]
-[[Category: Nucleotide-binding motif]]

1s1d: Difference between revisions

Latest revision as of 06:11, 23 August 2023

Structure and protein design of human apyrase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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