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Deciphering the d1 haem biosynthesis pathway and its relationship to a novel anaerobic route to protohaem

Reference	BB/E022944/1
Principal Investigator / Supervisor	Professor Stuart John Ferguson
Co-Investigators / Co-Supervisors	Dr Stephen Rigby, Professor Martin Warren, Dr Richard zajicek
Institution	University of Oxford
Department	Biochemistry
Funding type	Research
Value (£)	417,937
Status	Completed
Type	Research Grant
Start date	01/11/2007
End date	31/10/2010
Duration	36 months

Abstract

The cytochrome cd1 nitrite reductase, a vital enzyme of the denitrification part of the nitrogen cycle, contains a d1 haem (actually a dioxoisobacteriochlorin) for which the biosynthesis pathway represents almost the last unknown in porphyrin biological chemistry. Recent evidence indicates that two catalysts of this pathway are shared with an emerging uncharacterised pathway for anaerobic haem synthesis that occurs in archaea and sulfate reducing bacteria. We will characterise these two catalysts by a multidisciplinary approach that will establish the extent of the similarities between proteins from denitrifiers on the one hand and sulfate reducers/archea on the other. The outcome has potentially vey intriguing evolutionary implications. This will be followed by an attack with similar approaches on elucidating the other steps on the two pathways.

Summary

Many proteins contain haem (eg hemoglobin of the blood) which is a ring molecule with an iron atom in the middle. In some proteins the haem is modified, as is the case in an enzyme that catalyses a key reaction in the global nitrogen cycle. This reaction is reduction of nitrite to nitric oxide and the modified haem is called d1. We know a great deal about how 'standard' haem (protohaem) is made in cells from much simpler chemicals but we know almost nothing about how the vital d1 haem is made. It is our major aim to discover the steps whereby cells construct the d1 haem species. Unexpectedly, it has recently emerged that certain kinds of organisms classified as archaea do not have a recognisable haem synthesis pathway and the same is true for bacteria that reduce sulfate. The two classes of organisms do not contain nitrite reductase but do contain some predicted proteins which are very similar to those implicated in d1 haem synthesis. Thus we expect also to contribute to understanding a novel haem synthesis route with which interesting evolutionary implications are associated.

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Microbiology, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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