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8fw3

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Revision as of 12:10, 23 October 2024 by OCA (Talk | contribs)

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MtrR from Neisseria gonorrhoeae bound to Testosterone

Structural highlights

8fw3 is a 4 chain structure with sequence from Neisseria gonorrhoeae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.22Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MTRR_NEIGO Controls the permeability of the cell envelope to hydrophobic compounds such as antibiotics and detergents (PubMed:8196548). Represses transcription of the mtrCDE-encoded efflux pump by binding within the mtrCDE promoter (PubMed:9209024, PubMed:23221802). Also negatively regulates the expression of farR, by binding to its promoter region, leading indirectly to the positive regulation of expression of the farAB-encoded efflux pump (PubMed:14645274).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Transcriptional regulator MtrR inhibits the expression of the multidrug efflux pump operon mtrCDE in the pathogenic bacterium Neisseria gonorrhoeae. Here, we show that MtrR binds the hormonal steroids progesterone, beta-estradiol, and testosterone, which are present at urogenital infection sites, as well as ethinyl estrogen, a component of some hormonal contraceptives. Steroid binding leads to the decreased affinity of MtrR for cognate DNA, increased mtrCDE expression, and enhanced antimicrobial resistance. Furthermore, we solve crystal structures of MtrR bound to each steroid, thus revealing their binding mechanisms and the conformational changes that induce MtrR.

Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR.,Hooks GM, Ayala JC, Holley CL, Dhulipala V, Beggs GA, Perfect JR, Schumacher MA, Shafer WM, Brennan RG Nat Commun. 2024 Feb 7;15(1):1153. doi: 10.1038/s41467-024-45195-1. PMID:38326294^[5]

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

References

↑ Lee EH, Rouquette-Loughlin C, Folster JP, Shafer WM. FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR regulatory mechanism. J Bacteriol. 2003 Dec;185(24):7145-52. doi: 10.1128/jb.185.24.7145-7152.2003. PMID:14645274 doi:http://dx.doi.org/10.1128/jb.185.24.7145-7152.2003
↑ Zalucki YM, Dhulipala V, Shafer WM. Dueling regulatory properties of a transcriptional activator (MtrA) and repressor (MtrR) that control efflux pump gene expression in Neisseria gonorrhoeae. MBio. 2012 Dec 4;3(6):e00446-12. doi: 10.1128/mBio.00446-12. PMID:23221802 doi:http://dx.doi.org/10.1128/mBio.00446-12
↑ Pan W, Spratt BG. Regulation of the permeability of the gonococcal cell envelope by the mtr system. Mol Microbiol. 1994 Feb;11(4):769-75. doi: 10.1111/j.1365-2958.1994.tb00354.x. PMID:8196548 doi:http://dx.doi.org/10.1111/j.1365-2958.1994.tb00354.x
↑ Lucas CE, Balthazar JT, Hagman KE, Shafer WM. The MtrR repressor binds the DNA sequence between the mtrR and mtrC genes of Neisseria gonorrhoeae. J Bacteriol. 1997 Jul;179(13):4123-8. doi: 10.1128/jb.179.13.4123-4128.1997. PMID:9209024 doi:http://dx.doi.org/10.1128/jb.179.13.4123-4128.1997
↑ Hooks GM, Ayala JC, Holley CL, Dhulipala V, Beggs GA, Perfect JR, Schumacher MA, Shafer WM, Brennan RG. Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR. Nat Commun. 2024 Feb 7;15(1):1153. PMID:38326294 doi:10.1038/s41467-024-45195-1