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2mmt

From Proteopedia

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Current revision

Lasso peptide-based integrin inhibitor: Microcin J25 variant with RGDF substitution of Gly12-Ile13-Gly14-Thr15

Structural highlights

2mmt is a 1 chain structure with sequence from Escherichia coli. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rintoul MR, de Arcuri BF, Salomon RA, Farias RN, Morero RD. The antibacterial action of microcin J25: evidence for disruption of cytoplasmic membrane energization in Salmonella newport. FEMS Microbiol Lett. 2001 Nov 13;204(2):265-70. PMID:11731133
↑ Delgado MA, Rintoul MR, Farias RN, Salomon RA. Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25. J Bacteriol. 2001 Aug;183(15):4543-50. PMID:11443089 doi:http://dx.doi.org/10.1128/JB.183.15.4543-4550.2001
↑ Yuzenkova J, Delgado M, Nechaev S, Savalia D, Epshtein V, Artsimovitch I, Mooney RA, Landick R, Farias RN, Salomon R, Severinov K. Mutations of bacterial RNA polymerase leading to resistance to microcin j25. J Biol Chem. 2002 Dec 27;277(52):50867-75. Epub 2002 Oct 24. PMID:12401787 doi:http://dx.doi.org/10.1074/jbc.M209425200
↑ Hegemann JD, De Simone M, Zimmermann M, Knappe TA, Xie X, Di Leva FS, Marinelli L, Novellino E, Zahler S, Kessler H, Marahiel MA. Rational Improvement of the Affinity and Selectivity of Integrin Binding of Grafted Lasso Peptides. J Med Chem. 2014 Jun 27. PMID:24949551 doi:http://dx.doi.org/10.1021/jm5004478

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2mmt"

@@ Line 1: / Line 1: @@
 ==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]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='2mmt' size='340' side='right'caption='[[2mmt]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2mmt]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MMT FirstGlance]. <br>
+<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='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=2mmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mmt OCA], [http://pdbe.org/2mmt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mmt RCSB], [http://www.ebi.ac.uk/pdbsum/2mmt PDBsum]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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 ==
-[[http://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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Hegemann, J D]]
+[[Category: Escherichia coli]]
-[[Category: Knappe, T A]]
+[[Category: Large Structures]]
-[[Category: Marahiel, M A]]
+[[Category: Hegemann JD]]
-[[Category: Xie, X]]
+[[Category: Knappe TA]]
-[[Category: Zimmermann, M]]
+[[Category: Marahiel MA]]
-[[Category: Antibiotic]]
+[[Category: Xie X]]
-[[Category: Drug design]]
+[[Category: Zimmermann M]]
-[[Category: Epitope grafting]]
-[[Category: Integrin inhibitor]]
-[[Category: Lasso peptide]]
-[[Category: Molecular dynamic]]
-[[Category: Molecular scaffold]]

2mmt

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Current revision

Lasso peptide-based integrin inhibitor: Microcin J25 variant with RGDF substitution of Gly12-Ile13-Gly14-Thr15

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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