Database accession: MF7000250
Name: MarR protein Rv2887 (Mycobacterium tuberculosis)
PDB ID: 5x7z
Experimental method: X-ray (2.20 Å)
Assembly: Homodimer
Source organism: Mycobacterium tuberculosis
Primary publication of the structure:
Gao YR, Li DF, Fleming J, Zhou YF, Liu Y, Deng JY, Zhou L, Zhou J, Zhu GF, Zhang XE, Wang DC, Bi LJ
Structural analysis of the regulatory mechanism of MarR protein Rv2887 in M. tuberculosis.
(2017) Sci Rep 7: 6471
PMID: 28743871
Abstract:
MarR family proteins are transcriptional regulators that control expression of bacterial proteins involved in metabolism, virulence, stress responses and multi-drug resistance, mainly via ligand-mediated attenuation of DNA binding. Greater understanding of their underlying regulatory mechanism may open up new avenues for the effective treatment of bacterial infections. To gain molecular insight into the mechanism of Rv2887, a MarR family protein in M. tuberculosis, we first showed that it binds salicylate (SA) and para-aminosalicylic acid (PAS), its structural analogue and an antitubercular drug, in a 1:1 stoichiometry with high affinity. Subsequent determination and analysis of Rv2887 crystal structures in apo form, and in complex with SA, PAS and DNA showed that SA and PAS bind to Rv2887 at similar sites, and that Rv2887 interacts with DNA mainly by insertion of helix α4 into the major groove. Ligand binding triggers rotation of the wHTH domain of Rv2887 toward the dimerization domain, causing changes in protein conformation such that it can no longer bind to a 27 bp recognition sequence in the upstream region of gene Rv0560c. The structures provided here lay a foundation for the design of small molecules that target Rv2887, a potential new approach for the development of anti-mycobacterials.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA binding DNA binding
DNA-binding transcription factor activity DNA-binding transcription factor activity
Biological process:
regulation of DNA-templated transcription regulation of DNA-templated transcription
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, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: HTH-type transcriptional repressor Rv2887
Source organism: Mycobacterium tuberculosis
Length: 139 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGLADDAPLGYLLYRVGAVLRPEVSAALSPLGLTLPEFVCLRMLSQSPGLSSAELARHASVTPQAMNTVLRKLEDAGAVARPASVSSGRSLPATLTARGRALAKRAEAVVRAADARVLARLTAPQQREFKRMLEKLGSD
UniProtKB AC: P9WME9 (positions: 7-138)
Coverage: 94%
Name: HTH-type transcriptional repressor Rv2887
Source organism: Mycobacterium tuberculosis
Length: 139 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGLADDAPLGYLLYRVGAVLRPEVSAALSPLGLTLPEFVCLRMLSQSPGLSSAELARHASVTPQAMNTVLRKLEDAGAVARPASVSSGRSLPATLTARGRALAKRAEAVVRAADARVLARLTAPQQREFKRMLEKLGSD
UniProtKB AC: P9WME9 (positions: 7-138)
Coverage: 94%
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 I) transcriptional regulator
Evidence level: Direct evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
The MarR-type family transcriptional regulator, NadR is dimeric in solution (SE-HPLC/MALLS) as other MarR faimily proteins (PMID:18272181). Compared to ligand-stabilized holo-NadR, apo-NadR displayed an intrinsic flexibility focused in the DNA-binding region (PMID:27105075). The structural features of several family members have been described, they all have two subdomains: there is a helix-turn-helix (HTH) DNA-binding domain plus dimerization helices that form an interlocked dimerization domain. Dimerization is mediated by helices α1, α5, and α6 from each monomer resulting in an interlocked, tight dimer burying a large, hydrophobic solvent-accessible surface area. The structure of the dimerization region reveals domain swapping, where α1 of one subunit is inserted between α5′ and α6′ of the other subunit and forms a coiled coil with helix α6′ (PMID:19586910). The DNA-binding elements contain helices α3-α4 and strands β1-β2 from each monomer (PMID:29794028, PMID:35367827).
Chain A:
N/A
Chain A-2:
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)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
