3FRQ: Structure Of The Macrolide Biosensor Protein, Mphr(a), With Erythromcyin

The regulatory protein MphR(A) has recently seen extensive use in synthetic biological applications, such as metabolite sensing and exogenous control of gene expression. This protein negatively regulates the expression of a macrolide 2'-phosphotransferase I resistance gene (mphA) via binding to a 35-bp DNA operator upstream of the start codon and is de-repressed by the presence of erythromycin. Here, we present the refined crystal structure of the MphR(A) protein free of erythromycin and that of the MphR(A) protein with bound erythromycin at 2.00- and 1.76-A resolutions, respectively. We also studied the DNA binding properties of the protein and identified mutants of MphR(A) that are defective in gene repression and ligand binding in a cell-based reporter assay. The combination of these two structures illustrates the molecular basis of erythromycin-induced gene expression and provides a framework for additional applied uses of this protein in the isolation and engineered biosynthesis of polyketide natural products.
PDB ID: 3FRQDownload
MMDB ID: 70408
PDB Deposition Date: 2009/1/8
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.76  Å
Source Organism:
Similar Structures:
Biological Unit for 3FRQ: dimeric; determined by author and by software (PISA)
Molecular Components in 3FRQ
Label Count Molecule
Proteins (2 molecules)
Repressor Protein Mphr(a)
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB