6b2p: Difference between revisions

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-'''Unreleased structure'''
-The entry 6b2p is ON HOLD
+==Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis==
+<StructureSection load='6b2p' size='340' side='right' caption='[[6b2p]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6b2p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B2P FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CJJ:5-{5-chloro-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl}thiophene-2-sulfonamide'>CJJ</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b2p OCA], [http://pdbe.org/6b2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b2p RCSB], [http://www.ebi.ac.uk/pdbsum/6b2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b2p ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PKNB_MYCTO PKNB_MYCTO]] Protein kinase that regulates many aspects of mycobacterial physiology. Is a key component of a signal transduction pathway that regulates cell growth, cell shape and cell division via phosphorylation of target proteins.[UniProtKB:P9WI81]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (Ki approximately 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 muM (1-2 mug/mL) against the H37Ra isolate of M. tuberculosis.
-Authors: Zuccola, H.J.
+Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions.,Wang T, Bemis G, Hanzelka B, Zuccola H, Wynn M, Moody CS, Green J, Locher C, Liu A, Gao H, Xu Y, Wang S, Wang J, Bennani YL, Thomson JA, Muh U ACS Med Chem Lett. 2017 Nov 28;8(12):1224-1229. doi:, 10.1021/acsmedchemlett.7b00239. eCollection 2017 Dec 14. PMID:29259738<ref>PMID:29259738</ref>
-Description: Dual Inhibition of the Essential Protein Kinases A and B in Mycobacterium tuberculosis
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Zuccola, H.J]]
+<div class="pdbe-citations 6b2p" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Zuccola, H J]]
+[[Category: Drug design]]
+[[Category: Kinase]]
+[[Category: Transferase-inhibitor complex]]
+[[Category: Tuberculosis]]