Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Subray S. Hegde; Matthew W. Vetting; Steven L. Roderick; Lesley A. Mitchenall; Anthony Maxwell; Howard E. Takiff; John S. Blanchard

doi:10.1126/science.1110699

Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Subray S. Hegde, Matthew W. Vetting, Steven L. Roderick, Lesley A. Mitchenall, Anthony Maxwell, Howard E. Takiff, John S. Blanchard

Biochemistry

Research output: Contribution to journal › Article › peer-review

232 Scopus citations

Abstract

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 β 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.

Original language	English (US)
Pages (from-to)	1480-1483
Number of pages	4
Journal	Science
Volume	308
Issue number	5727
DOIs	https://doi.org/10.1126/science.1110699
State	Published - Jun 3 2005

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/science.1110699

Cite this

@article{e0e96bd2b9ba4ac9ad9ba844b72fbbc1,

title = "Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA",

abstract = "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 β 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.",

author = "Hegde, {Subray S.} and Vetting, {Matthew W.} and Roderick, {Steven L.} and Mitchenall, {Lesley A.} and Anthony Maxwell and Takiff, {Howard E.} and Blanchard, {John S.}",

year = "2005",

month = jun,

day = "3",

doi = "10.1126/science.1110699",

language = "English (US)",

volume = "308",

pages = "1480--1483",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5727",

}

TY - JOUR

T1 - Biochemistry

T2 - A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

AU - Hegde, Subray S.

AU - Vetting, Matthew W.

AU - Roderick, Steven L.

AU - Mitchenall, Lesley A.

AU - Maxwell, Anthony

AU - Takiff, Howard E.

AU - Blanchard, John S.

PY - 2005/6/3

Y1 - 2005/6/3

N2 - 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 β 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.

AB - 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 β 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.

UR - http://www.scopus.com/inward/record.url?scp=20344367084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20344367084&partnerID=8YFLogxK

U2 - 10.1126/science.1110699

DO - 10.1126/science.1110699

M3 - Article

C2 - 15933203

AN - SCOPUS:20344367084

SN - 0036-8075

VL - 308

SP - 1480

EP - 1483

JO - Science

JF - Science

IS - 5727

ER -

Biochemistry: A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this