View source for 9sme


==Crystal structure of CD73 in complex with JMS04-14, a pyrimidine-based nucleoside bisphosphonate inhibitor, in the closed state and in crystal form III==
<StructureSection load='9sme' size='340' side='right'caption='[[9sme]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9sme]] 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=9SME OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SME FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JOZ:[[(2~{R},3~{S},4~{R},5~{R})-5-[(4~{E})-3-methyl-2-oxidanylidene-4-phenylmethoxyimino-pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]methylphosphonic+acid'>A1JOZ</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=9sme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9sme OCA], [https://pdbe.org/9sme PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9sme RCSB], [https://www.ebi.ac.uk/pdbsum/9sme PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9sme ProSAT]</span></td></tr>
</table>
== 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.
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ecto-5'-nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression is associated with various aggressive cancers, including triple-negative breast cancer (TNBC) and pancreatic cancer, making it a promising target for diagnostic imaging. Besides antibodies, small-molecule CD73 inhibitors have been developed and are currently in clinical trials. This study aimed to develop and evaluate fluorine-18 labeled high-affinity CD73 inhibitors as tracers for the non-invasive positron emission tomography (PET) imaging of CD73 expression in cancer. Two CD73 inhibitors were selected for radiolabeling based on their high potency (K(i) values of ca. 1 nM) and favorable pharmacokinetic properties, yielding [(18)F]PSB-19427 ([(18)F]1) and [(18)F]MRS-4648 ([(18)F]2). Ex vivo imaging studies on human breast cancer tissues indicated specific binding of both radiotracers. Subsequent in vivo studies proved [(18)F]1 to be superior due to its long elimination half-life and its accumulation in TNBC and pancreatic cancer tissues, suggesting its potential as a versatile PET tracer for imaging of various solid tumors. Compared to [(18)F]FDG, [(18)F]1 was superior in visualizing TNBC, offering potential advantages over [(18)F]FDG in terms of specificity and diagnostic accuracy. Thus, [(18)F]1 is a PET tracer with outstanding properties suitable for broad application in cancer diagnosis and personalized medicine.

Fluorine-18-Labeled Nucleotide Analogs Targeting Ecto-5'-Nucleotidase (CD73) for Positron Emission Tomography Imaging of Solid Tumors.,Dobelmann C, Schmies CC, Rolshoven GW, Scortichini M, Wagner S, Isaak A, Idris RM, Dabel J, Grey L, Losenkova K, Moschutz S, Hroub HA, Keim A, Hoppner S, Sandholm J, Bostrom P, Hollmen M, Strater N, Hermann S, Yegutkin GG, Jacobson KA, Schelhaas S, Muller CE, Junker A Angew Chem Int Ed Engl. 2026 Apr 20;65(17):e22758. doi: 10.1002/anie.202522758. , Epub 2026 Mar 15. PMID:41834421<ref>PMID:41834421</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9sme" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Junker A]]
[[Category: Moschuetz S]]
[[Category: Muller CE]]
[[Category: Strater N]]