2f7c: Difference between revisions

Revision as of 18:18, 21 February 2008

CatM effector binding domain with its effector cis,cis-muconate

OverviewOverview

BenM, a bacterial transcriptional regulator, responds synergistically to two effectors, benzoate and cis,cis-muconate. CatM, a paralog with overlapping function, responds only to muconate. Structures of their effector-binding domains revealed two effector-binding sites in BenM. BenM and CatM are the first LysR-type regulators to be structurally characterized while bound with physiologically relevant exogenous inducers. The effector complexes were obtained by soaking crystals with stabilizing solutions containing high effector concentrations and minimal amounts of competing ions. This strategy, including data collection with fragments of fractured crystals, may be generally applicable to related proteins. In BenM and CatM, the binding of muconate to an interdomain pocket was facilitated by helix dipoles that provide charge stabilization. In BenM, benzoate also bound in an adjacent hydrophobic region where it alters the effect of muconate bound in the primary site. A charge relay system within the BenM protein appears to underlie synergistic transcriptional activation. According to this model, Glu162 is a pivotal residue that forms salt-bridges with different arginine residues depending on the occupancy of the secondary effector-binding site. Glu162 interacts with Arg160 in the absence of benzoate and with Arg146 when benzoate is bound. This latter interaction enhances the negative charge of muconate bound to the adjacent primary effector-binding site. The redistribution of the electrostatic potential draws two domains of the protein more closely towards muconate, with the movement mediated by the dipole moments of four alpha helices. Therefore, with both effectors, BenM achieves a unique conformation capable of high level transcriptional activation.

About this StructureAbout this Structure

2F7C is a Single protein structure of sequence from Acinetobacter baylyi with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Distinct effector-binding sites enable synergistic transcriptional activation by BenM, a LysR-type regulator., Ezezika OC, Haddad S, Clark TJ, Neidle EL, Momany C, J Mol Biol. 2007 Mar 30;367(3):616-29. Epub 2006 Oct 4. PMID:17291527

Page seeded by OCA on Thu Feb 21 17:18:32 2008

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-[[Image:2f7c.jpg|left|200px]]<br /><applet load="2f7c" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2f7c.jpg|left|200px]]<br /><applet load="2f7c" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2f7c, resolution 2.162&Aring;" />
 '''CatM effector binding domain with its effector cis,cis-muconate'''<br />
 ==Overview==
-BenM, a bacterial transcriptional regulator, responds synergistically to, two effectors, benzoate and cis,cis-muconate. CatM, a paralog with, overlapping function, responds only to muconate. Structures of their, effector-binding domains revealed two effector-binding sites in BenM. BenM, and CatM are the first LysR-type regulators to be structurally, characterized while bound with physiologically relevant exogenous, inducers. The effector complexes were obtained by soaking crystals with, stabilizing solutions containing high effector concentrations and minimal, amounts of competing ions. This strategy, including data collection with, fragments of fractured crystals, may be generally applicable to related, proteins. In BenM and CatM, the binding of muconate to an interdomain, pocket was facilitated by helix dipoles that provide charge stabilization., In BenM, benzoate also bound in an adjacent hydrophobic region where it, alters the effect of muconate bound in the primary site. A charge relay, system within the BenM protein appears to underlie synergistic, transcriptional activation. According to this model, Glu162 is a pivotal, residue that forms salt-bridges with different arginine residues depending, on the occupancy of the secondary effector-binding site. Glu162 interacts, with Arg160 in the absence of benzoate and with Arg146 when benzoate is, bound. This latter interaction enhances the negative charge of muconate, bound to the adjacent primary effector-binding site. The redistribution of, the electrostatic potential draws two domains of the protein more closely, towards muconate, with the movement mediated by the dipole moments of four, alpha helices. Therefore, with both effectors, BenM achieves a unique, conformation capable of high level transcriptional activation.
+BenM, a bacterial transcriptional regulator, responds synergistically to two effectors, benzoate and cis,cis-muconate. CatM, a paralog with overlapping function, responds only to muconate. Structures of their effector-binding domains revealed two effector-binding sites in BenM. BenM and CatM are the first LysR-type regulators to be structurally characterized while bound with physiologically relevant exogenous inducers. The effector complexes were obtained by soaking crystals with stabilizing solutions containing high effector concentrations and minimal amounts of competing ions. This strategy, including data collection with fragments of fractured crystals, may be generally applicable to related proteins. In BenM and CatM, the binding of muconate to an interdomain pocket was facilitated by helix dipoles that provide charge stabilization. In BenM, benzoate also bound in an adjacent hydrophobic region where it alters the effect of muconate bound in the primary site. A charge relay system within the BenM protein appears to underlie synergistic transcriptional activation. According to this model, Glu162 is a pivotal residue that forms salt-bridges with different arginine residues depending on the occupancy of the secondary effector-binding site. Glu162 interacts with Arg160 in the absence of benzoate and with Arg146 when benzoate is bound. This latter interaction enhances the negative charge of muconate bound to the adjacent primary effector-binding site. The redistribution of the electrostatic potential draws two domains of the protein more closely towards muconate, with the movement mediated by the dipole moments of four alpha helices. Therefore, with both effectors, BenM achieves a unique conformation capable of high level transcriptional activation.
 ==About this Structure==
-F7C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baylyi Acinetobacter baylyi] with SO4 and CCU as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F7C OCA].
+F7C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baylyi Acinetobacter baylyi] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=CCU:'>CCU</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F7C OCA].
 ==Reference==
-Distinct Effector-binding Sites Enable Synergistic Transcriptional Activation by BenM, a LysR-type Regulator., Ezezika OC, Haddad S, Clark TJ, Neidle EL, Momany C, J Mol Biol. 2007 Mar 30;367(3):616-29. Epub 2006 Oct 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17291527 17291527]
+Distinct effector-binding sites enable synergistic transcriptional activation by BenM, a LysR-type regulator., Ezezika OC, Haddad S, Clark TJ, Neidle EL, Momany C, J Mol Biol. 2007 Mar 30;367(3):616-29. Epub 2006 Oct 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17291527 17291527]
 [[Category: Acinetobacter baylyi]]
 [[Category: Single protein]]
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 [[Category: muconate]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:24:31 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:18:32 2008''