1f91

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1f91, resolution 2.4Å

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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 OH and DKA 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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