1uyv: Difference between revisions

Revision as of 16:29, 21 February 2008

ACETYL-COA CARBOXYLASE CARBOXYLTRANSFERASE DOMAIN L1705I/ V1967I MUTANT

OverviewOverview

Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty acids, making these enzymes important targets for the development of therapeutics against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of ACC is the site of action of commercial herbicides, such as haloxyfop, diclofop, and sethoxydim. We have determined the crystal structures at up to 2.5-A resolution of the CT domain of yeast ACC in complex with the herbicide haloxyfop or diclofop. The inhibitors are bound in the active site, at the interface of the dimer of the CT domain. Unexpectedly, inhibitor binding requires large conformational changes for several residues in this interface, which create a highly conserved hydrophobic pocket that extends deeply into the core of the dimer. Two residues that affect herbicide sensitivity are located in this binding site, and mutation of these residues disrupts the structure of the domain. Other residues in the binding site are strictly conserved among the CT domains.

About this StructureAbout this Structure

1UYV is a Single protein structure of sequence from Saccharomyces cerevisiae. Active as Acetyl-CoA carboxylase, with EC number 6.4.1.2 Full crystallographic information is available from OCA.

ReferenceReference

Molecular basis for the inhibition of the carboxyltransferase domain of acetyl-coenzyme-A carboxylase by haloxyfop and diclofop., Zhang H, Tweel B, Tong L, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5910-5. Epub 2004 Apr 12. PMID:15079078

Page seeded by OCA on Thu Feb 21 15:29:50 2008

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OCA

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-[[Image:1uyv.gif|left|200px]]<br /><applet load="1uyv" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1uyv.gif|left|200px]]<br /><applet load="1uyv" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1uyv, resolution 2.60&Aring;" />
 '''ACETYL-COA CARBOXYLASE CARBOXYLTRANSFERASE DOMAIN L1705I/ V1967I MUTANT'''<br />
 ==Overview==
-Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty, acids, making these enzymes important targets for the development of, therapeutics against obesity, diabetes, and other diseases. The, carboxyltransferase (CT) domain of ACC is the site of action of commercial, herbicides, such as haloxyfop, diclofop, and sethoxydim. We have, determined the crystal structures at up to 2.5-A resolution of the CT, domain of yeast ACC in complex with the herbicide haloxyfop or diclofop., The inhibitors are bound in the active site, at the interface of the dimer, of the CT domain. Unexpectedly, inhibitor binding requires large, conformational changes for several residues in this interface, which, create a highly conserved hydrophobic pocket that extends deeply into the, core of the dimer. Two residues that affect herbicide sensitivity are, located in this binding site, and mutation of these residues disrupts the, structure of the domain. Other residues in the binding site are strictly, conserved among the CT domains.
+Acetyl-CoA carboxylases (ACCs) are crucial for the metabolism of fatty acids, making these enzymes important targets for the development of therapeutics against obesity, diabetes, and other diseases. The carboxyltransferase (CT) domain of ACC is the site of action of commercial herbicides, such as haloxyfop, diclofop, and sethoxydim. We have determined the crystal structures at up to 2.5-A resolution of the CT domain of yeast ACC in complex with the herbicide haloxyfop or diclofop. The inhibitors are bound in the active site, at the interface of the dimer of the CT domain. Unexpectedly, inhibitor binding requires large conformational changes for several residues in this interface, which create a highly conserved hydrophobic pocket that extends deeply into the core of the dimer. Two residues that affect herbicide sensitivity are located in this binding site, and mutation of these residues disrupts the structure of the domain. Other residues in the binding site are strictly conserved among the CT domains.
 ==About this Structure==
-UYV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/Acetyl-CoA_carboxylase Acetyl-CoA carboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.4.1.2 6.4.1.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UYV OCA].
+UYV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/Acetyl-CoA_carboxylase Acetyl-CoA carboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.4.1.2 6.4.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UYV OCA].
 ==Reference==
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 [[Category: mutant]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:21:46 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:29:50 2008''