Publication Date:
2001-12-12
Description:
The Staphylococcus aureus multidrug binding protein QacR represses transcription of the qacA multidrug transporter gene and is induced by structurally diverse cationic lipophilic drugs. Here, we report the crystal structures of six QacR-drug complexes. Compared to the DNA bound structure, drug binding elicits a coil-to-helix transition that causes induction and creates an expansive multidrug-binding pocket, containing four glutamates and multiple aromatic and polar residues. These structures indicate the presence of separate but linked drug-binding sites within a single protein. This multisite drug-binding mechanism is consonant with studies on multidrug resistance transporters.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schumacher, M A -- Miller, M C -- Grkovic, S -- Brown, M H -- Skurray, R A -- Brennan, R G -- AI 48593/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 7;294(5549):2158-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11739955" target="_blank"〉PubMed〈/a〉
Keywords:
Bacterial Proteins/chemistry/metabolism
;
Berberine/chemistry/metabolism
;
Binding Sites
;
Crystallization
;
Crystallography, X-Ray
;
DNA/metabolism
;
Dequalinium/chemistry/metabolism
;
Dimerization
;
Drug Resistance, Multiple, Bacterial
;
Ethidium/chemistry/metabolism
;
Gentian Violet/chemistry/*metabolism
;
Glutamates/chemistry
;
Heterocyclic Compounds/chemistry/*metabolism
;
Hydrogen Bonding
;
Hydrophobic and Hydrophilic Interactions
;
Models, Molecular
;
Molecular Structure
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Repressor Proteins/*chemistry/metabolism
;
Rhodamines/chemistry/metabolism
;
Rosaniline Dyes/chemistry/*metabolism
;
Staphylococcus aureus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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