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'''Crystal Structure of PtlH with Fe/alpha ketoglutarate bound''' | '''Crystal Structure of PtlH with Fe/alpha ketoglutarate bound''' | ||
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[[Category: Omura, S.]] | [[Category: Omura, S.]] | ||
[[Category: You, Z.]] | [[Category: You, Z.]] | ||
[[Category: | [[Category: Dioxygenase]] | ||
[[Category: | [[Category: Double stranded barrel helix]] | ||
[[Category: | [[Category: Oxidoreductase]] | ||
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Revision as of 13:42, 4 May 2008
Crystal Structure of PtlH with Fe/alpha ketoglutarate bound
Overview
The non-heme iron dioxygenase PtlH from the soil organism Streptomyces avermitilis is a member of the iron(II)/alpha-ketoglutarate-dependent dioxygenase superfamily and catalyzes an essential reaction in the biosynthesis of the sesquiterpenoid antibiotic pentalenolactone. To investigate the structural basis for substrate recognition and catalysis, we have determined the x-ray crystal structure of PtlH in several complexes with the cofactors iron, alpha-ketoglutarate, and the non-reactive enantiomer of the substrate, ent-1-deoxypentalenic acid, in four different crystal forms to up to 1.31 A resolution. The overall structure of PtlH forms a double-stranded barrel helix fold, and the cofactor-binding site for iron and alpha-ketoglutarate is similar to other double-stranded barrel helix fold enzymes. Additional secondary structure elements that contribute to the substrate-binding site in PtlH are not conserved in other double-stranded barrel helix fold enzymes. Binding of the substrate enantiomer induces a reorganization of the monoclinic crystal lattice leading to a disorder-order transition of a C-terminal alpha-helix. The newly formed helix blocks the major access to the active site and effectively traps the bound substrate. Kinetic analysis of wild type and site-directed mutant proteins confirms a critical function of two arginine residues in substrate binding, while simulated docking of the enzymatic reaction product reveals the likely orientation of bound substrate.
About this Structure
2RDQ is a Single protein structure of sequence from Streptomyces avermitilis. Full crystallographic information is available from OCA.
Reference
Crystal structure of the non-heme iron dioxygenase PtlH in pentalenolactone biosynthesis., You Z, Omura S, Ikeda H, Cane DE, Jogl G, J Biol Chem. 2007 Dec 14;282(50):36552-60. Epub 2007 Oct 16. PMID:17942405 Page seeded by OCA on Sun May 4 16:42:26 2008