5k4p

From Proteopedia

(Difference between revisions)

Current revision

Catalytic Domain of MCR-1 phosphoethanolamine transferase

Structural highlights

5k4p is a 1 chain structure with sequence from Escherichia coli BL21(DE3). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.318Å
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

BACKGROUND: Due to the paucity of novel antibiotics, colistin has become a last resort antibiotic for treating multidrug resistant bacteria. Colistin acts by binding the lipid A component of lipopolysaccharides and subsequently disrupting the bacterial membrane. The recently identified plasmid-encoded MCR-1 enzyme is the first transmissible colistin resistance determinant and is a cause for concern for the spread of this resistance trait. MCR-1 is a phosphoethanolamine transferase that catalyzes the addition of phosphoethanolamine to lipid A to decrease colistin affinity. RESULTS: The structure of the catalytic domain of MCR-1 at 1.32 A reveals the active site is similar to that of related phosphoethanolamine transferases. CONCLUSIONS: The putative nucleophile for catalysis, threonine 285, is phosphorylated in cMCR-1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. As noted for catalytic domains of other phosphoethanolamine transferases, binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the cMCR-1 structure, suggesting that they are present in the membrane domain.

Structure of the catalytic domain of the colistin resistance enzyme MCR-1.,Stojanoski V, Sankaran B, Prasad BV, Poirel L, Nordmann P, Palzkill T BMC Biol. 2016 Sep 21;14(1):81. PMID:27655155^[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
↑ Stojanoski V, Sankaran B, Prasad BV, Poirel L, Nordmann P, Palzkill T. Structure of the catalytic domain of the colistin resistance enzyme MCR-1. BMC Biol. 2016 Sep 21;14(1):81. PMID:27655155 doi:http://dx.doi.org/10.1186/s12915-016-0303-0

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/5k4p"

Categories: Large Structures | Palzkill T | Prasad BVV | Sankaran B | Stojanoski V

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5k4p is ON HOLD
+==Catalytic Domain of MCR-1 phosphoethanolamine transferase==
+<StructureSection load='5k4p' size='340' side='right'caption='[[5k4p]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5k4p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K4P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K4P 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]] 1.318&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SOR:D-SORBITOL'>SOR</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5k4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k4p OCA], [https://pdbe.org/5k4p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k4p RCSB], [https://www.ebi.ac.uk/pdbsum/5k4p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k4p ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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 ==
+BACKGROUND: Due to the paucity of novel antibiotics, colistin has become a last resort antibiotic for treating multidrug resistant bacteria. Colistin acts by binding the lipid A component of lipopolysaccharides and subsequently disrupting the bacterial membrane. The recently identified plasmid-encoded MCR-1 enzyme is the first transmissible colistin resistance determinant and is a cause for concern for the spread of this resistance trait. MCR-1 is a phosphoethanolamine transferase that catalyzes the addition of phosphoethanolamine to lipid A to decrease colistin affinity. RESULTS: The structure of the catalytic domain of MCR-1 at 1.32 A reveals the active site is similar to that of related phosphoethanolamine transferases. CONCLUSIONS: The putative nucleophile for catalysis, threonine 285, is phosphorylated in cMCR-1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. As noted for catalytic domains of other phosphoethanolamine transferases, binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the cMCR-1 structure, suggesting that they are present in the membrane domain.
-Authors:
+Structure of the catalytic domain of the colistin resistance enzyme MCR-1.,Stojanoski V, Sankaran B, Prasad BV, Poirel L, Nordmann P, Palzkill T BMC Biol. 2016 Sep 21;14(1):81. PMID:27655155<ref>PMID:27655155</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5k4p" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Palzkill T]]
+[[Category: Prasad BVV]]
+[[Category: Sankaran B]]
+[[Category: Stojanoski V]]

5k4p

From Proteopedia

Current revision

Catalytic Domain of MCR-1 phosphoethanolamine transferase

Structural highlights

Function

Publication Abstract from PubMed

References

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