5grr

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Crystal structure of MCR-1

Structural highlights

5grr is a 1 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 1.45Å
Ligands:GOL, ZN
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

The newly identified mobile colistin resistant gene (mcr-1) rapidly spread among different bacterial strains and confers colistin resistance to its host, which has become a global concern. Based on sequence alignment, MCR-1 should be a phosphoethanolamine transferase, members of the YhjW/YjdB/YijP superfamily and catalyze the addition of phosphoethanolamine to lipid A, which needs to be validated experimentally. Here we report the first high-resolution crystal structure of the C-terminal catalytic domain of MCR-1 (MCR-1C) in its native state. The active pocket of native MCR-1C depicts unphosphorylated nucleophilic residue Thr285 in coordination with two Zinc ions and water molecules. A flexible adjacent active site loop (aa: Lys348-365) pose an open conformation compared to its structural homologues, suggesting of an open substrate entry channel. Taken together, this structure sets ground for further study of substrate binding and MCR-1 catalytic mechanism in development of potential therapeutic agents.

High resolution crystal structure of the catalytic domain of MCR-1.,Ma G, Zhu Y, Yu Z, Ahmad A, Zhang H Sci Rep. 2016 Dec 21;6:39540. doi: 10.1038/srep39540. PMID:28000749[3]

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

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References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Ma G, Zhu Y, Yu Z, Ahmad A, Zhang H. High resolution crystal structure of the catalytic domain of MCR-1. Sci Rep. 2016 Dec 21;6:39540. doi: 10.1038/srep39540. PMID:28000749 doi:http://dx.doi.org/10.1038/srep39540

Contents


PDB ID 5grr

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