Anaerobic, NADH-Dependent Haem Breakdown in a Family of Haemoproteins
Many pathogens function by internalising the haem molecules of their host organism and breaking down the porphyrin scaffold to sequester the Fe
Computational results suggested that the HemS homologues, HmuS, ChuS and ShuS, were also capable of promoting anaerobic haem breakdown, but that catalysis by ChuS and ShuS may be limited by competing functions. Bioinformatics was used to gauge what these possible alternative functions could be, and to place HemS within its wider phylogenetic context. The computational predictions were then tested in the laboratory. The three homologues were all shown to engage in the reductive haem breakdown process but to varying degrees of efficacy. These findings demonstrate that this novel haem breakdown reaction is not unique to HemS, but instead is a feature of a wider class of haemoproteins. A subset of these haemoproteins are known to bind certain DNA promoter regions, suggesting not only that they can catalytically degrade haem, but that they are also involved in transcriptional modulation responding to haem flux. Many of the bacterial species responsible for this class of protein (including those that produce HemS, ChuS and ShuS) are known to specifically target oxygen-depleted regions of the gastrointestinal tract. A deeper understanding of anaerobic haem breakdown processes engaged in by these pathogens could therefore prove useful in the development of future strategies for disease prevention.