1qfl
From Proteopedia
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BIOSYNTHETIC THIOLASE FROM ZOOGLOEA RAMIGERA IN COMPLEX WITH A REACTION INTERMEDIATE.
Overview
BACKGROUND: Thiolases are ubiquitous and form a large family of dimeric or, tetrameric enzymes with a conserved, five-layered alphabetaalphabetaalpha, catalytic domain. Thiolases can function either degradatively, in the, beta-oxidation pathway of fatty acids, or biosynthetically. Biosynthetic, thiolases catalyze the biological Claisen condensation of two molecules of, acetyl-CoA to form acetoacetyl-CoA. This is one of the fundamental, categories of carbon skeletal assembly patterns in biological systems and, is the first step in a wide range of biosynthetic pathways, including, those that generate cholesterol, steroid hormones, and various, energy-storage molecules. RESULTS: The crystal structure of the tetrameric, biosynthetic thiolase from Zoogloea ramigera has been determined at 2.0 A, resolution. The structure contains a striking and novel 'cage-like', tetramerization motif, which allows for some hinge motion of the two tight, dimers with respect to each other. The protein crystals were flash-frozen, after a short soak with the enzyme's substrate, acetoacetyl-CoA. A, reaction intermediate was thus trapped: the enzyme tetramer is acetylated, at Cys89 and has a CoA molecule bound in each of its active-site pockets., CONCLUSIONS: The shape of the substrate-binding pocket reveals the basis, for the short-chain substrate specificity of the enzyme. The active-site, architecture, and in particular the position of the covalently attached, acetyl group, allow a more detailed reaction mechanism to be proposed in, which Cys378 is involved in both steps of the reaction. The structure also, suggests an important role for the thioester oxygen atom of the acetylated, enzyme in catalysis.
About this Structure
1QFL is a Single protein structure of sequence from Zoogloea ramigera with SO4 and COA as ligands. Active as Acetyl-CoA C-acetyltransferase, with EC number 2.3.1.9 Structure known Active Sites: AS1, AS2, AS3 and AS4. Full crystallographic information is available from OCA.
Reference
A biosynthetic thiolase in complex with a reaction intermediate: the crystal structure provides new insights into the catalytic mechanism., Modis Y, Wierenga RK, Structure. 1999 Oct 15;7(10):1279-90. PMID:10545327
Page seeded by OCA on Mon Nov 5 16:59:43 2007
