View source for 7q52


==Crystal structure of S/T protein kinase PknG from Mycobacterium tuberculosis in complex with inhibitor L2W==
<StructureSection load='7q52' size='340' side='right'caption='[[7q52]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7q52]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q52 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q52 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8ZC:2-azanyl-3-(4-fluorophenyl)carbonyl-indolizine-1-carboxamide'>8ZC</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=7q52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q52 OCA], [https://pdbe.org/7q52 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q52 RCSB], [https://www.ebi.ac.uk/pdbsum/7q52 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q52 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PKNG_MYCTU PKNG_MYCTU] Phosphorylates GarA. May play a role in metabolic regulation via control of the phosphorylation status of GarA. Plays a crucial role in the survival of mycobacteria within host macrophages, by blocking the intracellular degradation of mycobacteria in lysosomes. Required for intrinsic antibiotic resistance.<ref>PMID:19019160</ref> <ref>PMID:19528288</ref> <ref>PMID:19638631</ref> <ref>PMID:17616581</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Computer-aided drug discovery methods play a major role in the development of therapeutically important small molecules, but their performance needs to be improved. Molecular dynamics simulations in mixed solvents are useful in understanding protein-ligand recognition and improving molecular docking predictions. In this work, we used ethanol as a cosolvent to find relevant interactions for ligands toward protein kinase G, an essential protein of Mycobacterium tuberculosis (Mtb). We validated the hot spots by screening a database of fragment-like compounds and another one of known kinase inhibitors. Next, we performed a pharmacophore-guided docking simulation and found three low micromolar inhibitors, including one with a novel chemical scaffold that we expanded to four derivative compounds. Binding affinities were characterized by intrinsic fluorescence quenching assays, isothermal titration calorimetry, and the analysis of melting curves. The predicted binding mode was confirmed by X-ray crystallography. Finally, the compounds significantly inhibited the viability of Mtb in infected THP-1 macrophages.

Cosolvent Sites-Based Discovery of Mycobacterium Tuberculosis Protein Kinase G Inhibitors.,Burastero O, Defelipe LA, Gola G, Tateosian NL, Lopez ED, Martinena CB, Arcon JP, Traian MD, Wetzler DE, Bento I, Barril X, Ramirez J, Marti MA, Garcia-Alai MM, Turjanski AG J Med Chem. 2022 Jun 23. doi: 10.1021/acs.jmedchem.1c02012. PMID:35737472<ref>PMID:35737472</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7q52" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Bento I]]
[[Category: Burastero O]]
[[Category: Defelipe LA]]
[[Category: Garcia-Alai MM]]