7daw: Difference between revisions

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-'''Unreleased structure'''
-The entry 7daw is ON HOLD
+==Crystal structure of Mycobacterium tuberculosis phenylalanyl-tRNA synthetase==
+<StructureSection load='7daw' size='340' side='right'caption='[[7daw]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7daw]] is a 2 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=7DAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DAW 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]] 2.83&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7daw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7daw OCA], [https://pdbe.org/7daw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7daw RCSB], [https://www.ebi.ac.uk/pdbsum/7daw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7daw ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SYFA_MYCTU SYFA_MYCTU]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Mycobacteria tuberculosis (Mtb) remains the deadliest pathogenic bacteria worldwide. The search for new antibiotics to treat drug-sensitive as well as drug-resistant tuberculosis has become a priority. The essential enzyme phenylalanyl-tRNA synthetase (PheRS) is an antibacterial drug target because of the large differences between bacterial and human PheRS counterparts. In a high-throughput screening of 2148 bioactive compounds, PF-3845, which is a known inhibitor of human fatty acid amide hydrolase (FAAH), was identified inhibiting Mtb PheRS at K(i) ~0.73 +/- 0.06 microM. The inhibition mechanism was studied with enzyme kinetics, protein structural modelling and crystallography, in comparison to a PheRS inhibitor of the noted phenyl-thiazolylurea-sulfonamide class. The 2.3-A crystal structure of Mtb PheRS in complex with PF-3845 revealed its novel binding mode, in which a trifluoromethyl-pyridinylphenyl group occupies the Phe pocket while a piperidine-piperazine urea group binds into the ATP pocket through an interaction network enforced by a sulfate ion. It represents the first non-nucleoside bi-substrate competitive inhibitor of bacterial PheRS. PF-3845 inhibits the in vitro growth of Mtb H37Rv at ~24 microM, and the potency of PF-3845 increased against Mtb pheS-FDAS, suggesting on target activity in mycobacterial whole cells. PF-3845 does not inhibit human cytoplasmic or mitochondrial PheRS in biochemical assay, which can be explained from the crystal structures. Further medicinal chemistry efforts focused on the piperidine-piperazine urea moiety may result in the identification of a selective antibacterial lead compound.
-Authors: Xu, M., Zhang, X., Xu, L., Chen, S.
+Re-discovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis.,Wang H, Xu M, Engelhart CA, Zhang X, Yan B, Pan M, Xu Y, Fan S, Liu R, Xu L, Hua L, Schnappinger D, Chen S J Biol Chem. 2021 Jan 4:jbc.RA120.016477. doi: 10.1074/jbc.RA120.016477. PMID:33397709<ref>PMID:33397709</ref>
-Description: Crystal structure of Mycobacterium tuberculosis phenylalanyl-tRNA synthetase
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chen, S]]
+<div class="pdbe-citations 7daw" style="background-color:#fffaf0;"></div>
-[[Category: Zhang, X]]
-[[Category: Xu, M]]
+==See Also==
-[[Category: Xu, L]]
+*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
+[[Category: Chen S]]
+[[Category: Xu L]]
+[[Category: Xu M]]
+[[Category: Zhang X]]