6c9p: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6c9p is ON HOLD
+==Mycobacterium tuberculosis adenosine kinase bound to 6-methylmercaptopurine riboside==
+<StructureSection load='6c9p' size='340' side='right'caption='[[6c9p]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6c9p]] 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=6C9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C9P 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&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MTP:2-HYDROXYMETHYL-5-(6-METHYLSULFANYL-PURIN-9-YL)-TETRAHYDRO-FURAN-3,4-DIOL'>MTP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6c9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c9p OCA], [https://pdbe.org/6c9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c9p RCSB], [https://www.ebi.ac.uk/pdbsum/6c9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c9p ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ADOK_MYCTU ADOK_MYCTU] ATP dependent phosphorylation of adenosine to monophosphate derivatives (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogues that displayed inhibition constants ranging from 5 to 120 nM against the enzyme. Two of these compounds exhibited low micromolar activity against Mtb with half maximal effective inhibitory concentrations of 1.7 and 4.0 muM. Our selectivity and preliminary pharmacokinetic studies showed that the compounds possess a higher degree of specificity against MtbAdoK when compared with the human counterpart and are well tolerated in rodents, respectively. Finally, crystallographic studies showed the molecular basis of inhibition, potency, and selectivity and revealed the presence of a potentially therapeutically relevant cavity unique to the MtbAdoK homodimer.
-Authors:
+Structure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase.,Crespo RA, Dang Q, Zhou NE, Guthrie LM, Snavely TC, Dong W, Loesch KA, Suzuki T, You L, Wang W, O'Malley T, Parish T, Olsen DB, Sacchettini JC J Med Chem. 2019 Apr 19. doi: 10.1021/acs.jmedchem.9b00020. PMID:31002508<ref>PMID:31002508</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6c9p" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Adenosine kinase 3D structures|Adenosine kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis]]
+[[Category: Crespo RA]]