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| | <StructureSection load='7pb5' size='340' side='right'caption='[[7pb5]], [[Resolution|resolution]] 1.28Å' scene=''> | | <StructureSection load='7pb5' size='340' side='right'caption='[[7pb5]], [[Resolution|resolution]] 1.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7pb5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PB5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7pb5]] is a 1 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=7PB5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PB5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.28Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/5'-nucleotidase 5'-nucleotidase], with EC number [https://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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[https://proteopedia.org/fgij/fg.htm?mol=7pb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pb5 OCA], [https://pdbe.org/7pb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pb5 RCSB], [https://www.ebi.ac.uk/pdbsum/7pb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pb5 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=7pb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pb5 OCA], [https://pdbe.org/7pb5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pb5 RCSB], [https://www.ebi.ac.uk/pdbsum/7pb5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pb5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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.
| + | [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 == |
| - | [[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>
| + | [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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Scaletti, E R]] | + | [[Category: Scaletti ER]] |
| - | [[Category: Strater, N]] | + | [[Category: Strater N]] |
| - | [[Category: Ecto-5'-nucleotidase]]
| + | |
| - | [[Category: En]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Substrate]]
| + | |
| 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
Human ecto-5-nucleotidase (CD73) is involved in purinergic signalling, which influences a diverse range of biological processes. CD73 hydrolyses AMP and is the major control point for the levels of extracellular adenosine. Inhibitors of CD73 thus block the immunosuppressive action of adenosine, a promising approach for cancer immunotherapy. Interestingly, ADP and ATP are competitive inhibitors of CD73, with the most potent small-molecule inhibitors to date being non-hydrolysable ADP analogues. While AMP is the major substrate of the enzyme, CD73 has been reported to hydrolyse other 5'-nucleoside monophosphates. Based on a fragment screening campaign at the BESSY II synchrotron, we present the binding modes of various deoxyribo- and ribonucleoside monophosphates and of four additional fragments binding to the nucleoside binding site of the open form of the enzyme. Kinetic analysis of monophosphate hydrolysis shows that ribonucleotide substrates are favoured over their deoxyribose equivalents with AMP being the best substrate. We characterised the initial step of AMP hydrolysis, the binding mode of AMP to the open conformation of CD73 and compared that to other monophosphate substrates. In addition, the inhibitory activity of various bisphosphonic acid derivatives of nucleoside diphosphates was determined. Although AMPCP remains the most potent inhibitor, replacement of the adenine base with other purines or with pyrimidines increases the Ki value only between twofold and sixfold. On the other hand, these nucleobases offer new opportunities to attach substituents for improved pharmacological properties.
Substrate binding modes of purine and pyrimidine nucleotides to human ecto-5'-nucleotidase (CD73) and inhibition by their bisphosphonic acid derivatives.,Scaletti E, Huschmann FU, Mueller U, Weiss MS, Strater N Purinergic Signal. 2021 Aug 17. pii: 10.1007/s11302-021-09802-w. doi:, 10.1007/s11302-021-09802-w. PMID:34403084[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
- ↑ Scaletti E, Huschmann FU, Mueller U, Weiss MS, Strater N. Substrate binding modes of purine and pyrimidine nucleotides to human ecto-5'-nucleotidase (CD73) and inhibition by their bisphosphonic acid derivatives. Purinergic Signal. 2021 Aug 17. pii: 10.1007/s11302-021-09802-w. doi:, 10.1007/s11302-021-09802-w. PMID:34403084 doi:http://dx.doi.org/10.1007/s11302-021-09802-w
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