View source for 9bt3


==Crystal structure of Chorismate Mutase from Mycobacterium tuberculosis in complex with the cyclic peptide inhibitor L2.1 (triclinic form)==
<StructureSection load='9bt3' size='340' side='right'caption='[[9bt3]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9bt3]] is a 16 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=9BT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BT3 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</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=9bt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bt3 OCA], [https://pdbe.org/9bt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bt3 RCSB], [https://www.ebi.ac.uk/pdbsum/9bt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bt3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SCMU_MYCTU SCMU_MYCTU] Catalyzes the Claisen rearrangement of chorismate to prephenate. May play some role in the pathogenicity.<ref>PMID:15654876</ref> <ref>PMID:15737998</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The secreted Chorismate mutase enzyme of Mycobacterium tuberculosis (*MtbCM) is an underexplored potential target for the development of new antitubercular agents that are increasingly needed as antibiotic resistance rises in prevalence. As an enzyme suspected to be involved in virulence and host-pathogen interactions, disruption of its function could circumvent the difficulty of treating tuberculosis-infected granulomas. Drug development, however, is limited by novel ligand discovery. Currently, *MtbCM activity is measured by using a low throughput acid/base-mediated product derivatization absorbance assay. Here, we utilized an RNA-display affinity selection approach enabled by the Random Peptides Integrated Discovery (RaPID) system to screen a vast library of macrocyclic peptides (MCP) for novel *MtbCM ligands. Peptides identified from the RaPID selection, and analogs thereof identified by analyzing the selection population dynamics, produced a new class of *MtbCM inhibiting MCPs. Among these were two noteworthy "chorismides", whose binding modes were elucidated by X-ray crystallography. Both were potent inhibitors of the CM enzyme activity. One was identified as an allosteric binding peptide revealing a novel inhibition approach, while the other is an active-site binding peptide that when conjugated to a fluorescent probe allowed for the development of a series of alternative fluorescence-based ligand-displacement assays that can be utilized for the assessment of potential *MtbCM inhibitors.

Active- and Allosteric-Site Cyclic Peptide Inhibitors of Secreted M. tuberculosis Chorismate Mutase.,van Neer RHP, Dranchak PK, Aitha M, Liu L, Carlson EK, Jacobsen IE, Battaile K, Fang Y, Tao D, Rai G, Padia J, Lovell S, Suga H, Inglese J ACS Infect Dis. 2025 Feb 4. doi: 10.1021/acsinfecdis.4c00798. PMID:39903128<ref>PMID:39903128</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9bt3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Battaile KP]]
[[Category: Inglese J]]
[[Category: Liu L]]
[[Category: Lovell S]]