Structure and function of enzymes in heme biosynthesis

Institute of Microbiology, Technische Universität Braunschweig, Braunschweig D-38106, Germany.
Protein Science (Impact Factor: 2.85). 06/2010; 19(6):1137-61. DOI: 10.1002/pro.405
Source: PubMed

ABSTRACT Tetrapyrroles like hemes, chlorophylls, and cobalamin are complex macrocycles which play essential roles in almost all living organisms. Heme serves as prosthetic group of many proteins involved in fundamental biological processes like respiration, photosynthesis, and the metabolism and transport of oxygen. Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V-shaped glutamyl-tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the "Radical SAM enzyme" coproporphyrinogen III dehydrogenase. This review summarizes the current understanding of the structure-function relationship for all heme biosynthetic enzymes and their potential interactions in the cell.

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Available from: Joachim Reichelt, Aug 19, 2014
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    • "One intriguing possibility is that PBGS, which forms a large complex best categorized as a tetramer of homodimers, could, because of its size, serve as a scaffold for a multienzyme complex. The observation that PBGS can also assume a hexameric form [14] [26] may hint at its plastic role as a supramolecular assembly nucleation site. Resolution of these issues will require masterful research, but the results will be illuminating. "
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