1uyr
From Proteopedia
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==Overview== | ==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. .. | + | 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== | ==About this Structure== | ||
| - | 1UYR is a | + | 1UYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with D1L as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UYR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:41:32 2007'' |
Revision as of 11:36, 5 November 2007
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ACETYL-COA CARBOXYLASE CARBOXYLTRANSFERASE DOMAIN IN COMPLEX WITH INHIBITOR DICLOFOP
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.
About this Structure
1UYR is a Single protein structure of sequence from Saccharomyces cerevisiae with D1L as ligand. Active as Acetyl-CoA carboxylase, with EC number 6.4.1.2 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
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
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