3BTJ

crystal structure of QacR(E58Q) bound to dequalinium

Summary for 3BTJ

• Entry DOI: 10.2210/pdb3btj/pdb
• Related: 1jt6 1qvu 1rkw 3BT9 3BTC 3BTI
• Descriptor: HTH-type transcriptional regulator qacR, SULFATE ION, DEQUALINIUM, ... (4 entities in total)
• Functional Keywords: qacr, multidrug binding, dequalinium, bivalent drug, dna-binding, plasmid, repressor, transcription, transcription regulation
• Biological source: Staphylococcus aureus subsp. aureus Mu50
• Total number of polymer chains: 4
• Total formula weight: 90702.36

Authors

Schumacher, M.A.,Schuman, J.T.,Brennan, R.G. (deposition date: 2007-12-28, release date: 2008-08-12, Last modification date: 2023-08-30)

Primary citation

Peters, K.M.,Schuman, J.T.,Skurray, R.A.,Brown, M.H.,Brennan, R.G.,Schumacher, M.A.
QacR-cation recognition is mediated by a redundancy of residues capable of charge neutralization
Biochemistry, 47:8122-8129, 2008

PubMed Abstract: 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.

PubMed: 18616285
DOI: 10.1021/bi8008246

Experimental method

X-RAY DIFFRACTION (2.98 Å)