PDBsum entry 3btj

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Transcription PDB id
Protein chains
186 a.a. *
SO4 ×17
Waters ×6
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Crystal structure of qacr(e58q) bound to dequalinium
Structure: Hth-type transcriptional regulator qacr. Chain: b, d, a, e. Engineered: yes. Mutation: yes
Source: Staphylococcus aureus. Strain: mu50. Atcc: 700699. Gene: qacr. Expressed in: escherichia coli.
2.98Å     R-factor:   0.216     R-free:   0.264
Authors: M.A.Schumacher,J.T.Schuman,R.G.Brennan
Key ref: K.M.Peters et al. (2008). QacR-cation recognition is mediated by a redundancy of residues capable of charge neutralization. Biochemistry, 47, 8122-8129. PubMed id: 18616285
28-Dec-07     Release date:   12-Aug-08    
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Protein chains
Pfam   ArchSchema ?
P0A0N3  (QACR_STAAM) -  HTH-type transcriptional regulator QacR
188 a.a.
186 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     transcription, DNA-dependent   3 terms 
  Biochemical function     DNA binding     2 terms  


Biochemistry 47:8122-8129 (2008)
PubMed id: 18616285  
QacR-cation recognition is mediated by a redundancy of residues capable of charge neutralization.
K.M.Peters, J.T.Schuman, R.A.Skurray, M.H.Brown, R.G.Brennan, M.A.Schumacher.
The Staphylococcus aureus multidrug binding protein QacR binds to a broad spectrum of structurally dissimilar cationic, lipophilic drugs. Our previous structural analyses suggested that five QacR glutamic acid residues are critical for charge neutralization and specification of certain drugs. For example, E57 and E58 interact with berberine and with one of the positively charged moieties of the bivalent drug dequalinium. Here we report the structural and biochemical effects of substituting E57 and E58 with alanine and glutamine. Unexpectedly, individual substitutions of these residues did not significantly affect QacR drug binding affinity. Structures of QacR(E57Q) and QacR(E58Q) bound to dequalinium indicated that E57 and E58 are redundant for charge neutralization. The most significant finding was that berberine was reoriented in the QacR multidrug binding pocket so that its positive charge was neutralized by side chain oxygen atoms and aromatic residues. Together, these data emphasize the remarkable versatility of the QacR multidrug binding pocket, illustrating that the capacity of QacR to bind myriad cationic drugs is largely governed by the presence in the pocket of a redundancy of polar, charged, and aromatic residues that are capable of electrostatic neutralization.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21264225 K.M.Peters, B.E.Brooks, M.A.Schumacher, R.A.Skurray, R.G.Brennan, and M.H.Brown (2011).
A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity.
  PLoS One, 6, e15974.
PDB code: 3pm1
19819701 D.A.Gutmann, A.Ward, I.L.Urbatsch, G.Chang, and H.W.van Veen (2010).
Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1.
  Trends Biochem Sci, 35, 36-42.  
20580544 H.Wade (2010).
MD recognition by MDR gene regulators.
  Curr Opin Struct Biol, 20, 489-496.  
19324881 A.Hernández, M.J.Maté, P.C.Sánchez-Díaz, A.Romero, F.Rojo, and J.L.Martínez (2009).
Structural and Functional Analysis of SmeT, the Repressor of the Stenotrophomonas maltophilia Multidrug Efflux Pump SmeDEF.
  J Biol Chem, 284, 14428-14438.
PDB code: 2w53
19820093 M.Bellinzoni, S.Buroni, F.Schaeffer, G.Riccardi, E.De Rossi, and P.M.Alzari (2009).
Structural plasticity and distinct drug-binding modes of LfrR, a mycobacterial efflux pump regulator.
  J Bacteriol, 191, 7531-7537.
PDB codes: 2v57 2wgb
19715704 P.Zou, and H.S.McHaourab (2009).
Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA.
  J Mol Biol, 393, 574-585.  
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