8c25: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 8c25 is ON HOLD
+==purine nucleoside phosphorylase in complex with JS-375==
+<StructureSection load='8c25' size='340' side='right'caption='[[8c25]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8c25]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C25 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]] 1.56&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JU9:[(~{E})-2-[4-methoxy-2-[(4-oxidanylidene-3,5-dihydropyrrolo[3,2-d]pyrimidin-7-yl)sulfanyl]phenyl]ethenyl]phosphonic+acid'>JU9</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=8c25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c25 OCA], [https://pdbe.org/8c25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c25 RCSB], [https://www.ebi.ac.uk/pdbsum/8c25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c25 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A045IAS2_MYCTX A0A045IAS2_MYCTX] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. Cleaves guanosine, inosine, 2'-deoxyguanosine and 2'-deoxyinosine.[ARBA:ARBA00002678]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Purine nucleoside phosphorylase (PNP) is a well-known molecular target with potential therapeutic applications in the treatment of T-cell malignancies and/or bacterial/parasitic infections. Here, we report the design, development of synthetic methodology, and biological evaluation of a series of 30 novel PNP inhibitors based on acyclic nucleoside phosphonates bearing a 9-deazahypoxanthine nucleobase. The strongest inhibitors exhibited IC(50) values as low as 19 nM (human PNP) and 4 nM (Mycobacterium tuberculosis (Mt) PNP) and highly selective cytotoxicity toward various T-lymphoblastic cell lines with CC(50) values as low as 9 nM. No cytotoxic effect was observed on other cancer cell lines (HeLa S3, HL60, HepG2) or primary PBMCs for up to 10 muM. We report the first example of the PNP inhibitor exhibiting over 60-fold selectivity for the pathogenic enzyme (MtPNP) over hPNP. The results are supported by a crystallographic study of eight enzyme-inhibitor complexes and by ADMET profiling in vitro and in vivo.
-Authors: Djukic, S., Pachl, P., Rezacova, P.
+Design, Synthesis, Biological Evaluation, and Crystallographic Study of Novel Purine Nucleoside Phosphorylase Inhibitors.,Skacel J, Djukic S, Baszczynski O, Kalcic F, Bilek T, Chalupsky K, Kozak J, Dvorakova A, Tloust'ova E, Kral'ova Z, Smidkova M, Voldrich J, Rumlova M, Pachl P, Brynda J, Vuckova T, Fabry M, Snasel J, Pichova I, Rezacova P, Mertlikova-Kaiserova H, Janeba Z J Med Chem. 2023 May 25;66(10):6652-6681. doi: 10.1021/acs.jmedchem.2c02097. Epub , 2023 May 3. PMID:37134237<ref>PMID:37134237</ref>
-Description: purine nucleoside phosphorylase in complex with JS-375
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Pachl, P]]
+<div class="pdbe-citations 8c25" style="background-color:#fffaf0;"></div>
-[[Category: Rezacova, P]]
-[[Category: Djukic, S]]
+==See Also==
+*[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis]]
+[[Category: Djukic S]]
+[[Category: Pachl P]]
+[[Category: Rezacova P]]