Publication Date:
2005-06-04
Description:
Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral beta helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hegde, Subray S -- Vetting, Matthew W -- Roderick, Steven L -- Mitchenall, Lesley A -- Maxwell, Anthony -- Takiff, Howard E -- Blanchard, John S -- AI33696/AI/NIAID NIH HHS/ -- AI60899/AI/NIAID NIH HHS/ -- T32 AI007501/AI/NIAID NIH HHS/ -- T32 AI07501/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2005 Jun 3;308(5727):1480-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15933203" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Antitubercular Agents/chemistry/*pharmacology
;
Bacterial Proteins/chemistry/*physiology
;
Ciprofloxacin/pharmacology
;
Crystallography, X-Ray
;
DNA Gyrase/metabolism
;
DNA, Bacterial/*chemistry
;
DNA, Superhelical/chemistry
;
*Drug Resistance, Bacterial
;
Drug Resistance, Microbial/*physiology
;
Enzyme Inhibitors/chemistry
;
Escherichia coli/enzymology
;
Fluoroquinolones/antagonists & inhibitors/chemistry/*pharmacology
;
Models, Molecular
;
*Molecular Mimicry
;
Molecular Sequence Data
;
Monomeric GTP-Binding Proteins
;
Mycobacterium tuberculosis/drug effects/*physiology
;
Protein Conformation
;
Protein Folding
;
Structure-Activity Relationship
;
Topoisomerase II Inhibitors
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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