2hh7: Difference between revisions

Revision as of 18:41, 21 February 2008

Crystal Structure of Cu(I) bound CsoR from Mycobacterium tuberculosis.

OverviewOverview

Copper is an essential element that becomes highly cytotoxic when concentrations exceed the capacity of cells to sequester the ion. Here, we identify a new copper-specific repressor (CsoR) of a copper-sensitive operon (cso) in Mycobacterium tuberculosis (Mtb) that is representative of a large, previously uncharacterized family of proteins (DUF156). Electronic and X-ray absorption spectroscopies reveal that CsoR binds a single-monomer mole equivalent of Cu(I) to form a trigonally coordinated (S(2)N) Cu(I) complex. The 2.6-A crystal structure of copper-loaded CsoR shows a homodimeric antiparallel four-helix bundle architecture that represents a novel DNA-binding fold. The Cu(I) is coordinated by Cys36, Cys65' and His61' in a subunit bridging site. Cu(I) binding negatively regulates the binding of CsoR to a DNA fragment encompassing the operator-promoter region of the Mtb cso operon; this results in derepression of the operon in Mtb and the heterologous host Mycobacterium smegmatis. Substitution of Cys36 or His61 with alanine abolishes Cu(I)- and CsoR-dependent regulation in vivo and in vitro. Potential roles of CsoR in Mtb pathogenesis are discussed.

About this StructureAbout this Structure

2HH7 is a Single protein structure of sequence from Mycobacterium tuberculosis with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator., Liu T, Ramesh A, Ma Z, Ward SK, Zhang L, George GN, Talaat AM, Sacchettini JC, Giedroc DP, Nat Chem Biol. 2007 Jan;3(1):60-8. Epub 2006 Dec 3. PMID:17143269

Page seeded by OCA on Thu Feb 21 17:41:50 2008

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OCA

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-[[Image:2hh7.gif|left|200px]]<br /><applet load="2hh7" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2hh7.gif|left|200px]]<br /><applet load="2hh7" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2hh7, resolution 2.55&Aring;" />
 '''Crystal Structure of Cu(I) bound CsoR from Mycobacterium tuberculosis.'''<br />
 ==Overview==
-Copper is an essential element that becomes highly cytotoxic when, concentrations exceed the capacity of cells to sequester the ion. Here, we, identify a new copper-specific repressor (CsoR) of a copper-sensitive, operon (cso) in Mycobacterium tuberculosis (Mtb) that is representative of, a large, previously uncharacterized family of proteins (DUF156)., Electronic and X-ray absorption spectroscopies reveal that CsoR binds a, single-monomer mole equivalent of Cu(I) to form a trigonally coordinated, (S(2)N) Cu(I) complex. The 2.6-A crystal structure of copper-loaded CsoR, shows a homodimeric antiparallel four-helix bundle architecture that, represents a novel DNA-binding fold. The Cu(I) is coordinated by Cys36, Cys65' and His61' in a subunit bridging site. Cu(I) binding negatively, regulates the binding of CsoR to a DNA fragment encompassing the, operator-promoter region of the Mtb cso operon; this results in, derepression of the operon in Mtb and the heterologous host Mycobacterium, smegmatis. Substitution of Cys36 or His61 with alanine abolishes Cu(I)-, and CsoR-dependent regulation in vivo and in vitro. Potential roles of, CsoR in Mtb pathogenesis are discussed.
+Copper is an essential element that becomes highly cytotoxic when concentrations exceed the capacity of cells to sequester the ion. Here, we identify a new copper-specific repressor (CsoR) of a copper-sensitive operon (cso) in Mycobacterium tuberculosis (Mtb) that is representative of a large, previously uncharacterized family of proteins (DUF156). Electronic and X-ray absorption spectroscopies reveal that CsoR binds a single-monomer mole equivalent of Cu(I) to form a trigonally coordinated (S(2)N) Cu(I) complex. The 2.6-A crystal structure of copper-loaded CsoR shows a homodimeric antiparallel four-helix bundle architecture that represents a novel DNA-binding fold. The Cu(I) is coordinated by Cys36, Cys65' and His61' in a subunit bridging site. Cu(I) binding negatively regulates the binding of CsoR to a DNA fragment encompassing the operator-promoter region of the Mtb cso operon; this results in derepression of the operon in Mtb and the heterologous host Mycobacterium smegmatis. Substitution of Cys36 or His61 with alanine abolishes Cu(I)- and CsoR-dependent regulation in vivo and in vitro. Potential roles of CsoR in Mtb pathogenesis are discussed.
 ==About this Structure==
-HH7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with CU1 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2HH7 OCA].
+HH7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=CU1:'>CU1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HH7 OCA].
 ==Reference==
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 [[Category: Single protein]]
 [[Category: Ramesh, A.]]
-[[Category: Sacchettini,J.C.]]
+[[Category: Sacchettini,J C.]]
 [[Category: CU1]]
 [[Category: 4-helix bundle]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:46:09 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:41:50 2008''