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5ylf

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Revision as of 08:25, 22 February 2018

MCR-1 complex with D-glucose

Structural highlights

5ylf is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	5ylc, 5yle
Gene:	mcr1, mcr-1, APZ14_31440 ("Bacillus coli" Migula 1895)
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

Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable colistin-resistance gene (mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction. Mutation of the residues involved in ETA and d-glucose binding impairs colistin resistance in recombinant Escherichia coli containing full-length MCR-1. Partial analogs of the substrate are used for cocrystallization with cMCR-1, providing valuable information about the family of PEA transferases. One of the analogs, ETA, causes clear inhibition of polymyxin B resistance, highlighting its potential for drug development. These data demonstrate the crucial role of the PEA- and lipid A-binding pockets and provide novel insights into the structure-based mechanisms, important drug-target hot spots, and a drug template for further drug development to combat the urgent, rising threat of MCR-1-mediated antibiotic resistance.-Wei, P., Song, G., Shi, M., Zhou, Y., Liu, Y., Lei, J., Chen, P., Yin, L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.

Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance.,Wei P, Song G, Shi M, Zhou Y, Liu Y, Lei J, Chen P, Yin L FASEB J. 2017 Oct 27. pii: fj.201700705R. doi: 10.1096/fj.201700705R. PMID:29079699^[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
↑ Wei P, Song G, Shi M, Zhou Y, Liu Y, Lei J, Chen P, Yin L. Substrate analog interaction with MCR-1 offers insight into the rising threat of the plasmid-mediated transferable colistin resistance. FASEB J. 2017 Oct 27. pii: fj.201700705R. doi: 10.1096/fj.201700705R. PMID:29079699 doi:http://dx.doi.org/10.1096/fj.201700705R

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/5ylf"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ylf' size='340' side='right' caption='[[5ylf]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ylf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YLF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YLF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ylf]] is a 1 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=5YLF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YLF FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ylc|5ylc]], [[5yle|5yle]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ylf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ylf OCA], [http://pdbe.org/5ylf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ylf RCSB], [http://www.ebi.ac.uk/pdbsum/5ylf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ylf ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Bacillus coli migula 1895]]
 [[Category: Chen, P]]
 [[Category: Lei, J]]

5ylf

From Proteopedia

Revision as of 08:25, 22 February 2018

MCR-1 complex with D-glucose

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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