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| | <StructureSection load='4h1s' size='340' side='right'caption='[[4h1s]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4h1s' size='340' side='right'caption='[[4h1s]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4h1s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H1S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4h1s]] 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=4H1S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H1S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.2Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.5 3.1.3.5] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4h1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h1s OCA], [http://pdbe.org/4h1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h1s RCSB], [http://www.ebi.ac.uk/pdbsum/4h1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h1s ProSAT]</span></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=4h1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h1s OCA], [https://pdbe.org/4h1s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h1s RCSB], [https://www.ebi.ac.uk/pdbsum/4h1s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h1s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN]] Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN] Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN]] Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.<ref>PMID:21933152</ref> | + | [https://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN] Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.<ref>PMID:21933152</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 5'-nucleotidase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Heuts, D P]] | + | [[Category: Heuts DP]] |
| - | [[Category: Levy, C W]] | + | [[Category: Levy CW]] |
| - | [[Category: Olkhov, R V]] | + | [[Category: Olkhov RV]] |
| - | [[Category: Scrutton, N S]] | + | [[Category: Scrutton NS]] |
| - | [[Category: Shaw, A M]] | + | [[Category: Shaw AM]] |
| - | [[Category: Weissenborn, M J]] | + | [[Category: Weissenborn MJ]] |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Disease
5NTD_HUMAN Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
5NTD_HUMAN Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.[1]
Publication Abstract from PubMed
CD73 is a dimeric ecto-5'-nucleotidase that is expressed on the exterior side of the plasma membrane. CD73 has important regulatory functions in the extracellular metabolism of certain nucleoside monophosphates, in particular adenosine monophosphate, and has been linked to a number of pathological conditions such as cancer and myocardial ischaemia. Here, we present the crystal structure of a soluble form of human soluble CD73 (sCD73) at 2.2 A resolution, a truncated form of CD73 that retains ecto-5'-nucleotidase activity. With this structure we obtained insight into the dimerisation of CD73, active site architecture, and a sense of secondary modifications of the protein. The crystal structure reveals a conserved loop that is directly involved in the dimer-dimer interaction showing that the two subunits of the dimer are not linked by disulfide bridges. Using biophotonic microarray imaging we were able to confirm glycosylation of the enzyme and show that the enzyme is decorated with a variety of oligosaccharide structures. The crystal structure of sCD73 will aid the design of inhibitors or activator molecules for the treatment of several diseases and prove useful in explaining the possible roles of single nucleotide polymorphisms in physiology and disease.
Crystal Structure of a Soluble Form of Human CD73 with Ecto-5'-Nucleotidase Activity.,Heuts DP, Weissenborn MJ, Olkhov RV, Shaw AM, Levy C, Scrutton NS Chembiochem. 2012 Sep 20. doi: 10.1002/cbic.201200426. PMID:22997138[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garavaglia S, Bruzzone S, Cassani C, Canella L, Allegrone G, Sturla L, Mannino E, Millo E, De Flora A, Rizzi M. The high-resolution crystal structure of periplasmic Haemophilus influenzae NAD nucleotidase reveals a novel enzymatic function of human CD73 related to NAD metabolism. Biochem J. 2011 Sep 20. PMID:21933152 doi:10.1042/BJ20111263
- ↑ Heuts DP, Weissenborn MJ, Olkhov RV, Shaw AM, Levy C, Scrutton NS. Crystal Structure of a Soluble Form of Human CD73 with Ecto-5'-Nucleotidase Activity. Chembiochem. 2012 Sep 20. doi: 10.1002/cbic.201200426. PMID:22997138 doi:http://dx.doi.org/10.1002/cbic.201200426
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