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The Alternative Haem Biosynthesis Pathway: Structure, Function and Properties of Sirohaem Decarboxylase

Palmer, David James (2014) The Alternative Haem Biosynthesis Pathway: Structure, Function and Properties of Sirohaem Decarboxylase. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:47619)

Language: English
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Haem, a cyclic tetrapyrrole, is found in organisms from all three domains of life. Haem is a prosthetic group for many proteins involved in essential biological processes such as respiration and oxygen transport. Synthesis of haem in eukaryotes and most bacteria follows a well defined route with highly conserved intermediates. However, an alternative haem biosynthesis pathway in Archaea and some bacteria was recently elucidated. This newly discovered pathway utilises sirohaem as a metabolic intermediate rather than a prosthetic group.

This study focused on the AhbA and AhbB proteins from three sources, Desulfovibrio desulfuricans, Desulfovibrio vulgaris and Methanosarcina barkeri. Purifications of individual recombinantly produced proteins revealed that both AhbA and AhbB are highly unstable. However, low concentrations of D. desulfuricans and D. vulgaris AhbA and AhbB proteins were isolated and were discovered to have decarboxylase activity. Simultaneous overproduction of AhbA and AhbB proteins facilitated the co-purification of stable heteromeric AhbA/B complexes from all three organisms. However, despite their sequence similarities, distinctly different properties were observed between the homologues including differences in oliogmeric state and haem/product binding capabilities. The D. desulfuricans enzyme has been crystallised and its structure has been elucidated in both apo- and product-bound forms. Mutagenesis of the D. desulfuricans complex has provided further information about active site residues and a mechanism of action has been proposed. Finally, novel functional chimeric complexes were produced using the Desulfovibrio proteins.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Warren, Martin J.
Uncontrolled keywords: haem sirohaem biosynthesis enzymes
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Users 1 not found.
Date Deposited: 11 Mar 2015 01:00 UTC
Last Modified: 20 May 2021 13:33 UTC
Resource URI: (The current URI for this page, for reference purposes)
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