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2rdq

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Revision as of 09:24, 23 January 2008 by OCA (Talk | contribs)
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2rdq, resolution 1.310Å

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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 1.31A 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 with , and as ligands. 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

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