6li4

From Proteopedia

(Difference between revisions)

Revision as of 11:00, 22 November 2023

Crystal structure of MCR-1-S

Structural highlights

6li4 is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.78Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MCR1_ECOLX Probably catalyzes the addition of a phosphoethanolamine moiety to lipid A. Phosphoethanolamine modification of lipid A gives polymyxin resistance (PubMed:26603172).^[1] Confers resistance to polymyxin-type antibiotics; expression of the Mcr-1 protein in E.coli increases colistin and polymyxin B minimal inhibitory concentration (MIC) from 0.5 mg/ml to 2.0 mg/ml. The pHNSHP45 plasmid can transfer efficiently (0.1 to 0.001) to other E.coli strains by conjugation and increases polymxin MIC by 8- to 16-fold; it may not require selective pressure to be maintained in the cell. When transformed into K.pneumoniae or P.aeruginosa it also increases polymxin MIC 8- to 16-fold. In a murine (BALB/c mice) thigh infection study using an mcr1-encoding plasmid isolated from a human patient, the plasmid confers in vivo protection against colistin (PubMed:26603172).^[2]

Publication Abstract from PubMed

Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, blaMBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-beta-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of beta-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-beta-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs.

Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin.,Sun H, Zhang Q, Wang R, Wang H, Wong YT, Wang M, Hao Q, Yan A, Kao RY, Ho PL, Li H Nat Commun. 2020 Oct 16;11(1):5263. doi: 10.1038/s41467-020-18939-y. PMID:33067430^[3]

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

References

↑ Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016 Feb;16(2):161-8. doi: 10.1016/S1473-3099(15)00424-7. Epub, 2015 Nov 19. PMID:26603172 doi:http://dx.doi.org/10.1016/S1473-3099(15)00424-7
↑ Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016 Feb;16(2):161-8. doi: 10.1016/S1473-3099(15)00424-7. Epub, 2015 Nov 19. PMID:26603172 doi:http://dx.doi.org/10.1016/S1473-3099(15)00424-7
↑ Sun H, Zhang Q, Wang R, Wang H, Wong YT, Wang M, Hao Q, Yan A, Kao RY, Ho PL, Li H. Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin. Nat Commun. 2020 Oct 16;11(1):5263. doi: 10.1038/s41467-020-18939-y. PMID:33067430 doi:http://dx.doi.org/10.1038/s41467-020-18939-y

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/6li4"

Categories: Escherichia coli | Large Structures | Sun H | Wang M | Zhang Q

@@ Line 3: / Line 3: @@
 <StructureSection load='6li4' size='340' side='right'caption='[[6li4]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6li4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LI4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6li4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LI4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mcr1, mcr-1, APZ14_31440 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=6li4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li4 OCA], [https://pdbe.org/6li4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6li4 RCSB], [https://www.ebi.ac.uk/pdbsum/6li4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6li4 ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6li4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li4 OCA], [http://pdbe.org/6li4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6li4 RCSB], [http://www.ebi.ac.uk/pdbsum/6li4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6li4 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MCR1_ECOLX MCR1_ECOLX]] Probably catalyzes the addition of a phosphoethanolamine moiety to lipid A. Phosphoethanolamine modification of lipid A gives polymyxin resistance (PubMed:26603172).<ref>PMID:26603172</ref>   Confers resistance to polymyxin-type antibiotics; expression of the Mcr-1 protein in E.coli increases colistin and polymyxin B minimal inhibitory concentration (MIC) from 0.5 mg/ml to 2.0 mg/ml. The pHNSHP45 plasmid can transfer efficiently (0.1 to 0.001) to other E.coli strains by conjugation and increases polymxin MIC by 8- to 16-fold; it may not require selective pressure to be maintained in the cell. When transformed into K.pneumoniae or P.aeruginosa it also increases polymxin MIC 8- to 16-fold. In a murine (BALB/c mice) thigh infection study using an mcr1-encoding plasmid isolated from a human patient, the plasmid confers in vivo protection against colistin (PubMed:26603172).<ref>PMID:26603172</ref>
+[https://www.uniprot.org/uniprot/MCR1_ECOLX MCR1_ECOLX] Probably catalyzes the addition of a phosphoethanolamine moiety to lipid A. Phosphoethanolamine modification of lipid A gives polymyxin resistance (PubMed:26603172).<ref>PMID:26603172</ref>   Confers resistance to polymyxin-type antibiotics; expression of the Mcr-1 protein in E.coli increases colistin and polymyxin B minimal inhibitory concentration (MIC) from 0.5 mg/ml to 2.0 mg/ml. The pHNSHP45 plasmid can transfer efficiently (0.1 to 0.001) to other E.coli strains by conjugation and increases polymxin MIC by 8- to 16-fold; it may not require selective pressure to be maintained in the cell. When transformed into K.pneumoniae or P.aeruginosa it also increases polymxin MIC 8- to 16-fold. In a murine (BALB/c mice) thigh infection study using an mcr1-encoding plasmid isolated from a human patient, the plasmid confers in vivo protection against colistin (PubMed:26603172).<ref>PMID:26603172</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
 [[Category: Large Structures]]
-[[Category: Sun, H]]
+[[Category: Sun H]]
-[[Category: Wang, M]]
+[[Category: Wang M]]
-[[Category: Zhang, Q]]
+[[Category: Zhang Q]]
-[[Category: Antibiotic]]
-[[Category: Transferase]]

6li4

From Proteopedia

Revision as of 11:00, 22 November 2023

Crystal structure of MCR-1-S

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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