4.7 Review

Structural aspects of enzymes involved in prokaryotic Gram-positive heme biosynthesis

Journal

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
Volume 21, Issue -, Pages 3933-3945

Publisher

ELSEVIER
DOI: 10.1016/j.csbj.2023.07.024

Keywords

Coproporphyrin ferrochelatase; Coproheme decarboxylase; Frataxin; Coproporphyrinogen oxidase; Uroporphyrinogen decarboxylase; Structure determination; Molecular enzymology

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The coproporphyrin dependent heme biosynthesis pathway is predominantly used by Gram-positive bacteria. This pathway is of interest for basic research as it relates to medical biotechnology and the development of new antibiotic targets against Gram-positive superbugs. A review of the accumulated structural data on the enzymes involved in this pathway is provided, highlighting the need for further analysis and future research to gain a comprehensive understanding of prokaryotic heme biosynthesis.
The coproporphyrin dependent heme biosynthesis pathway is almost exclusively utilized by Gram-positive bacteria. This fact makes it a worthwhile topic for basic research, since a fundamental understanding of a metabolic pathway is necessary to translate the focus towards medical biotechnology, which is very relevant in this specific case, considering the need for new antibiotic targets to counteract the pathogenicity of Grampositive superbugs. Over the years a lot of structural data on the set of enzymes acting in Gram-positive heme biosynthesis has accumulated in the Protein Database (www.pdb.org). One major challenge is to filter and analyze all available structural information in sufficient detail in order to be helpful and to draw conclusions. Here we pursued to give a holistic overview of structural information on enzymes involved in the coproporphyrin dependent heme biosynthesis pathway. There are many aspects to be extracted from experimentally determined structures regarding the reaction mechanisms, where the smallest variation of the position of an amino acid residue might be important, but also on a larger level regarding protein-protein interactions, where the focus has to be on surface characteristics and subunit (secondary) structural elements and oligomerization. This review delivers a status quo, highlights still missing information, and formulates future research endeavors in order to better understand prokaryotic heme biosynthesis.

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