1f91
From Proteopedia
(New page: 200px<br /><applet load="1f91" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f91, resolution 2.4Å" /> '''BETA-KETOACYL-[ACYL-C...) |
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| - | [[Image:1f91.gif|left|200px]]<br /><applet load="1f91" size=" | + | [[Image:1f91.gif|left|200px]]<br /><applet load="1f91" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1f91, resolution 2.4Å" /> | caption="1f91, resolution 2.4Å" /> | ||
'''BETA-KETOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE I IN COMPLEX WITH C10 FATTY ACID SUBSTRATE'''<br /> | '''BETA-KETOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE I IN COMPLEX WITH C10 FATTY ACID SUBSTRATE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: beta-ketoacyl-acyl carrier protein synthase (KAS) I is vital | + | BACKGROUND: beta-ketoacyl-acyl carrier protein synthase (KAS) I is vital for the construction of the unsaturated fatty acid carbon skeletons characterizing E. coli membrane lipids. The new carbon-carbon bonds are created by KAS I in a Claisen condensation performed in a three-step enzymatic reaction. KAS I belongs to the thiolase fold enzymes, of which structures are known for five other enzymes. RESULTS: Structures of the catalytic Cys-Ser KAS I mutant with covalently bound C10 and C12 acyl substrates have been determined to 2.40 and 1.85 A resolution, respectively. The KAS I dimer is not changed by the formation of the complexes but reveals an asymmetric binding of the two substrates bound to the dimer. A detailed model is proposed for the catalysis of KAS I. Of the two histidines required for decarboxylation, one donates a hydrogen bond to the malonyl thioester oxo group, and the other abstracts a proton from the leaving group. CONCLUSIONS: The same mechanism is proposed for KAS II, which also has a Cys-His-His active site triad. Comparison to the active site architectures of other thiolase fold enzymes carrying out a decarboxylation step suggests that chalcone synthase and KAS III with Cys-His-Asn triads use another mechanism in which both the histidine and the asparagine interact with the thioester oxo group. The acyl binding pockets of KAS I and KAS II are so similar that they alone cannot provide the basis for their differences in substrate specificity. |
==About this Structure== | ==About this Structure== | ||
| - | 1F91 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with OH and DKA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-ketoacyl-acyl-carrier-protein_synthase_I Beta-ketoacyl-acyl-carrier-protein synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] Full crystallographic information is available from [http:// | + | 1F91 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=OH:'>OH</scene> and <scene name='pdbligand=DKA:'>DKA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Beta-ketoacyl-acyl-carrier-protein_synthase_I Beta-ketoacyl-acyl-carrier-protein synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F91 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Kadziola, A.]] | [[Category: Kadziola, A.]] | ||
[[Category: Larsen, S.]] | [[Category: Larsen, S.]] | ||
| - | [[Category: Olsen, J | + | [[Category: Olsen, J G.]] |
[[Category: Siggaard-Andersen, M.]] | [[Category: Siggaard-Andersen, M.]] | ||
| - | [[Category: Wettstein-Knowles, P | + | [[Category: Wettstein-Knowles, P V.]] |
[[Category: DKA]] | [[Category: DKA]] | ||
[[Category: OH]] | [[Category: OH]] | ||
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[[Category: thiolase fold family]] | [[Category: thiolase fold family]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:36:09 2008'' |
Revision as of 10:36, 21 February 2008
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BETA-KETOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE I IN COMPLEX WITH C10 FATTY ACID SUBSTRATE
Overview
BACKGROUND: beta-ketoacyl-acyl carrier protein synthase (KAS) I is vital for the construction of the unsaturated fatty acid carbon skeletons characterizing E. coli membrane lipids. The new carbon-carbon bonds are created by KAS I in a Claisen condensation performed in a three-step enzymatic reaction. KAS I belongs to the thiolase fold enzymes, of which structures are known for five other enzymes. RESULTS: Structures of the catalytic Cys-Ser KAS I mutant with covalently bound C10 and C12 acyl substrates have been determined to 2.40 and 1.85 A resolution, respectively. The KAS I dimer is not changed by the formation of the complexes but reveals an asymmetric binding of the two substrates bound to the dimer. A detailed model is proposed for the catalysis of KAS I. Of the two histidines required for decarboxylation, one donates a hydrogen bond to the malonyl thioester oxo group, and the other abstracts a proton from the leaving group. CONCLUSIONS: The same mechanism is proposed for KAS II, which also has a Cys-His-His active site triad. Comparison to the active site architectures of other thiolase fold enzymes carrying out a decarboxylation step suggests that chalcone synthase and KAS III with Cys-His-Asn triads use another mechanism in which both the histidine and the asparagine interact with the thioester oxo group. The acyl binding pockets of KAS I and KAS II are so similar that they alone cannot provide the basis for their differences in substrate specificity.
About this Structure
1F91 is a Single protein structure of sequence from Escherichia coli with and as ligands. Active as Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 Full crystallographic information is available from OCA.
Reference
Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery., Olsen JG, Kadziola A, von Wettstein-Knowles P, Siggaard-Andersen M, Larsen S, Structure. 2001 Mar 7;9(3):233-43. PMID:11286890
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