View source for 2mmt


==Lasso peptide-based integrin inhibitor: Microcin J25 variant with RGDF substitution of Gly12-Ile13-Gly14-Thr15==
<StructureSection load='2mmt' size='340' side='right'caption='[[2mmt]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mmt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MMT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</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=2mmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mmt OCA], [https://pdbe.org/2mmt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mmt RCSB], [https://www.ebi.ac.uk/pdbsum/2mmt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mmt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MCJA_ECOLX MCJA_ECOLX] Peptide antibiotic that functions through inhibition of the bacterial DNA-dependent RNA polymerase (RNAP). May inhibit transcription by binding in RNAP secondary channel and blocking nucleotide substrates access to the catalytic center. Exhibits potent bacteriocidal activity against a range of Enterobacteriaceae, including several pathogenic E.coli, Salmonella and Shigella strains. Also acts on the cytoplasmic membrane of Salmonella newport, producing alteration of membrane permeability and disruption of the subsequent gradient dissipation, which inhibits several processes essential for cell viability, such as oxygen consumption. Induces bacterial filamentation in susceptible cells in a non-SOS-dependent way, but this phenotype may result from impaired transcription of genes coding for cell division proteins.<ref>PMID:11731133</ref> <ref>PMID:11443089</ref> <ref>PMID:12401787</ref> 
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== Publication Abstract from PubMed ==
Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective alphavbeta3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).

Rational Improvement of the Affinity and Selectivity of Integrin Binding of Grafted Lasso Peptides.,Hegemann JD, De Simone M, Zimmermann M, Knappe TA, Xie X, Di Leva FS, Marinelli L, Novellino E, Zahler S, Kessler H, Marahiel MA J Med Chem. 2014 Jun 27. PMID:24949551<ref>PMID:24949551</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mmt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Hegemann JD]]
[[Category: Knappe TA]]
[[Category: Marahiel MA]]
[[Category: Xie X]]
[[Category: Zimmermann M]]