1t9c: Difference between revisions

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Crystal Structure Of Yeast Acetohydroxyacid Synthase In Complex With A Sulfonylurea Herbicide, Sulfometuron methyl

OverviewOverview

Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is the target for the sulfonylurea herbicides, which act as potent inhibitors of the enzyme. Chlorsulfuron (marketed as Glean) and sulfometuron methyl (marketed as Oust) are two commercially important members of this family of herbicides. Here we report crystal structures of yeast AHAS in complex with chlorsulfuron (at a resolution of 2.19 A), sulfometuron methyl (2.34 A), and two other sulfonylureas, metsulfuron methyl (2.29 A) and tribenuron methyl (2.58 A). The structures observed suggest why these inhibitors have different potencies and provide clues about the differential effects of mutations in the active site tunnel on various inhibitors. In all of the structures, the thiamin diphosphate cofactor is fragmented, possibly as the result of inhibitor binding. In addition to thiamin diphosphate, AHAS requires FAD for activity. Recently, it has been reported that reduction of FAD can occur as a minor side reaction due to reaction with the carbanion/enamine of the hydroxyethyl-ThDP intermediate that is formed midway through the catalytic cycle. Here we report that the isoalloxazine ring has a bent conformation that would account for its ability to accept electrons from the hydroxyethyl intermediate. Most sequence and mutation data suggest that yeast AHAS is a high-quality model for the plant enzyme.

About this StructureAbout this Structure

1T9C is a Single protein structure of sequence from Saccharomyces cerevisiae with , , , , and as ligands. Active as Acetolactate synthase, with EC number 2.2.1.6 Full crystallographic information is available from OCA.

ReferenceReference

Elucidating the specificity of binding of sulfonylurea herbicides to acetohydroxyacid synthase., McCourt JA, Pang SS, Guddat LW, Duggleby RG, Biochemistry. 2005 Feb 22;44(7):2330-8. PMID:15709745

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-[[Image:1t9c.gif|left|200px]]<br /><applet load="1t9c" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1t9c.gif|left|200px]]<br /><applet load="1t9c" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1t9c, resolution 2.34&Aring;" />
 '''Crystal Structure Of Yeast Acetohydroxyacid Synthase In Complex With A Sulfonylurea Herbicide, Sulfometuron methyl'''<br />
 ==Overview==
-Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is the target for the, sulfonylurea herbicides, which act as potent inhibitors of the enzyme., Chlorsulfuron (marketed as Glean) and sulfometuron methyl (marketed as, Oust) are two commercially important members of this family of herbicides., Here we report crystal structures of yeast AHAS in complex with, chlorsulfuron (at a resolution of 2.19 A), sulfometuron methyl (2.34 A), and two other sulfonylureas, metsulfuron methyl (2.29 A) and tribenuron, methyl (2.58 A). The structures observed suggest why these inhibitors have, different potencies and provide clues about the differential effects of, mutations in the active site tunnel on various inhibitors. In all of the, structures, the thiamin diphosphate cofactor is fragmented, possibly as, the result of inhibitor binding. In addition to thiamin diphosphate, AHAS, requires FAD for activity. Recently, it has been reported that reduction, of FAD can occur as a minor side reaction due to reaction with the, carbanion/enamine of the hydroxyethyl-ThDP intermediate that is formed, midway through the catalytic cycle. Here we report that the isoalloxazine, ring has a bent conformation that would account for its ability to accept, electrons from the hydroxyethyl intermediate. Most sequence and mutation, data suggest that yeast AHAS is a high-quality model for the plant enzyme.
+Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is the target for the sulfonylurea herbicides, which act as potent inhibitors of the enzyme. Chlorsulfuron (marketed as Glean) and sulfometuron methyl (marketed as Oust) are two commercially important members of this family of herbicides. Here we report crystal structures of yeast AHAS in complex with chlorsulfuron (at a resolution of 2.19 A), sulfometuron methyl (2.34 A), and two other sulfonylureas, metsulfuron methyl (2.29 A) and tribenuron methyl (2.58 A). The structures observed suggest why these inhibitors have different potencies and provide clues about the differential effects of mutations in the active site tunnel on various inhibitors. In all of the structures, the thiamin diphosphate cofactor is fragmented, possibly as the result of inhibitor binding. In addition to thiamin diphosphate, AHAS requires FAD for activity. Recently, it has been reported that reduction of FAD can occur as a minor side reaction due to reaction with the carbanion/enamine of the hydroxyethyl-ThDP intermediate that is formed midway through the catalytic cycle. Here we report that the isoalloxazine ring has a bent conformation that would account for its ability to accept electrons from the hydroxyethyl intermediate. Most sequence and mutation data suggest that yeast AHAS is a high-quality model for the plant enzyme.
 ==About this Structure==
-T9C 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 K, MG, 1SM, P23, FAD and P22 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetolactate_synthase Acetolactate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.2.1.6 2.2.1.6] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1T9C OCA].
+T9C 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 <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=1SM:'>1SM</scene>, <scene name='pdbligand=P23:'>P23</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=P22:'>P22</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetolactate_synthase Acetolactate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.2.1.6 2.2.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T9C OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Saccharomyces cerevisiae]]
 [[Category: Single protein]]
-[[Category: Duggleby, R.G.]]
+[[Category: Duggleby, R G.]]
-[[Category: Guddat, L.W.]]
+[[Category: Guddat, L W.]]
-[[Category: McCourt, J.A.]]
+[[Category: McCourt, J A.]]
-[[Category: Pang, S.S.]]
+[[Category: Pang, S S.]]
 [[Category: 1SM]]
 [[Category: FAD]]
@@ Line 33: / Line 33: @@
 [[Category: thiamin diphosphate]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:05:49 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:11:15 2008''