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Structural studies of 2,4'-dihydroxyacetophenone dioxygenase, calexcitin and two plant-like variants of 5-aminolaevulinic acid dehydratase

Structural studies of 2,4'-dihydroxyacetophenone dioxygenase, calexcitin and two plant-like variants of 5-aminolaevulinic acid dehydratase
Structural studies of 2,4'-dihydroxyacetophenone dioxygenase, calexcitin and two plant-like variants of 5-aminolaevulinic acid dehydratase

Microorganisms play a huge role in the breakdown of the hundreds of millions of tonnes of aromatic chemicals released into the environment every year. 2,4’-Dihydroxyacetophenone dioxygenase (DAD) is an enzyme form the soil bacterium Alcaligenes sp. Which cleaves its aromatic substrate in a novel way. The enzyme has been over-expressed in E. coli N-4830-1 cells and purified to homogeneity. Crystals grown from the purified protein diffracted X-rays to 1.1Ǻ resolution. Numerous attempts at solving the crystal structure of this enzyme, including the use of direct methods, molecular replacement and MAD phasing, have so far proved unsuccessful.

Calexcitin is one of the handful of proteins so far implicated in associative memory. Two separate DNA constructs specify the calexcitin gene from the long-finned squid Loligo pealei were made and the protein from each was over-expressed and purified. Crystal screens were successful, resulting in the collection of X-ray data to 2.1Ǻ resolution. Attempts at solving the crystal structure using molecular replacement and MAD/SAD phasing were unsuccessful.

The enzyme 5-aminolaevulinic acid dehydratase (ALAD) catalyses an early step in the synthesis of tetrapyrroles. Far less is understood about the mechanism of the plant-like variants of this enzyme than the zinc-dependent counterparts. Attempts were thus made at solving the crystal structure of two plant-like ALADs. The gene for Plasmodium falciparum ALAD was cloned into a pET11a vector in preparation for structural studies. The Chlorobium vibrioforme ALAD gene was cloned into a pET11a vector and the protein over-expressed and purified to homogeneity. X-Ray diffraction data to 2.6Ǻ resolution on crystals grown from the purified protein allowed the structure to be solved by molecular replacement, using the plant-like ALAD of Pseudomonas aeruginosa as a search model. The structure was refined to a final R-factor of 26.6% and Rfree of 34.8%.

University of Southampton
Beaven, Gordon
89d8ff78-606f-417d-957c-a54d82c16bcc
Beaven, Gordon
89d8ff78-606f-417d-957c-a54d82c16bcc

Beaven, Gordon (2005) Structural studies of 2,4'-dihydroxyacetophenone dioxygenase, calexcitin and two plant-like variants of 5-aminolaevulinic acid dehydratase. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Microorganisms play a huge role in the breakdown of the hundreds of millions of tonnes of aromatic chemicals released into the environment every year. 2,4’-Dihydroxyacetophenone dioxygenase (DAD) is an enzyme form the soil bacterium Alcaligenes sp. Which cleaves its aromatic substrate in a novel way. The enzyme has been over-expressed in E. coli N-4830-1 cells and purified to homogeneity. Crystals grown from the purified protein diffracted X-rays to 1.1Ǻ resolution. Numerous attempts at solving the crystal structure of this enzyme, including the use of direct methods, molecular replacement and MAD phasing, have so far proved unsuccessful.

Calexcitin is one of the handful of proteins so far implicated in associative memory. Two separate DNA constructs specify the calexcitin gene from the long-finned squid Loligo pealei were made and the protein from each was over-expressed and purified. Crystal screens were successful, resulting in the collection of X-ray data to 2.1Ǻ resolution. Attempts at solving the crystal structure using molecular replacement and MAD/SAD phasing were unsuccessful.

The enzyme 5-aminolaevulinic acid dehydratase (ALAD) catalyses an early step in the synthesis of tetrapyrroles. Far less is understood about the mechanism of the plant-like variants of this enzyme than the zinc-dependent counterparts. Attempts were thus made at solving the crystal structure of two plant-like ALADs. The gene for Plasmodium falciparum ALAD was cloned into a pET11a vector in preparation for structural studies. The Chlorobium vibrioforme ALAD gene was cloned into a pET11a vector and the protein over-expressed and purified to homogeneity. X-Ray diffraction data to 2.6Ǻ resolution on crystals grown from the purified protein allowed the structure to be solved by molecular replacement, using the plant-like ALAD of Pseudomonas aeruginosa as a search model. The structure was refined to a final R-factor of 26.6% and Rfree of 34.8%.

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Published date: 2005

Identifiers

Local EPrints ID: 465761
URI: http://eprints.soton.ac.uk/id/eprint/465761
PURE UUID: 799941bf-564f-47d6-88b7-a6cc6cc03932

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Date deposited: 05 Jul 2022 02:54
Last modified: 05 Jul 2022 02:54

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Author: Gordon Beaven

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