Database accession: MF7000752
Name: MepR (Staphylococcus aureus)
PDB ID: 3eco
Experimental method: X-ray (2.40 Å)
Assembly: Homodimer
Source organism: Staphylococcus aureus
Primary publication of the structure:
Kumaraswami M, Schuman JT, Seo SM, Kaatz GW, Brennan RG
Structural and biochemical characterization of MepR, a multidrug binding transcription regulator of the Staphylococcus aureus multidrug efflux pump MepA.
(2009) Nucleic Acids Res. 37: 1211-24
PMID: 19129225
Abstract:
MepR is a multidrug binding transcription regulator that represses expression of the Staphylococcus aureus multidrug efflux pump gene, mepA, as well as its own gene. MepR is induced by multiple cationic toxins, which are also substrates of MepA. In order to understand the gene regulatory and drug-binding mechanisms of MepR, we carried out biochemical, in vivo and structural studies. The 2.40 A resolution structure of drug-free MepR reveals the most open MarR family protein conformation to date, which will require a huge conformational change to bind cognate DNA. DNA-binding data show that MepR uses a dual regulatory binding mode as the repressor binds the mepA operator as a dimer of dimers, but binds the mepR operator as a single dimer. Alignment of the six half sites reveals the consensus MepR binding site, 5'-GTTAGAT-3'. 'Drug' binding studies show that MepR binds to ethidium and DAPI with comparable affinities (K(d) = 2.6 and 4.5 microM, respectively), but with significantly lower affinity to the larger rhodamine 6G (K(d) = 62.6 microM). Mapping clinically relevant or in vitro selected MepR mutants onto the MepR structure suggests that their defective repressor phenotypes are due to structural and allosteric defects.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA-binding transcription factor activity DNA-binding transcription factor activity
Biological process:
response to stress response to stress
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: HTH marR-type domain-containing protein
Source organism: Staphylococcus aureus
Length: 139 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEFTYSYLFRMISHEMKQKADQKLEQFDITNEQGHTLGYLYAHQQDGLTQNDIAKALQRTGPTVSNLLRNLERKKLIYRYVDAQDTRRKNIGLTTSGIKLVEAFTSIFDEMEQTLVSQLSEEENEQMKANLTKMLSSLQ
UniProtKB AC: A0A0H3JPT9 (positions: 3-139)
Coverage: 98%
Name: HTH marR-type domain-containing protein
Source organism: Staphylococcus aureus
Length: 139 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEFTYSYLFRMISHEMKQKADQKLEQFDITNEQGHTLGYLYAHQQDGLTQNDIAKALQRTGPTVSNLLRNLERKKLIYRYVDAQDTRRKNIGLTTSGIKLVEAFTSIFDEMEQTLVSQLSEEENEQMKANLTKMLSSLQ
UniProtKB AC: A0A0H3JPT9 (positions: 4-139)
Coverage: 97%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Winged helix DNA-binding domain (MarR type II) transcriptional regulator
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
Thermal unfolding measured with circular dichroism of the MarR family protein, HucR, suggested two-state model of unfolding (PMID:15448166). Also, a decrease in pH induced a molten globule-like state, where the protein remained in dimeric form (PMID:27282811). Helices 1, 2, 6 and 7 form the dimerization subdomain, they form an apparently stable dimer interface that preconfigures the DNA recognition HTH subdomain for DNA binding (PMID:16750221).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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