Porphyrin Binding and Distortion and Substrate Specificity in the Ferrochelatase Reaction: The Role of Active Site Residues

Karlberg, T.; Hansson, Mattias; Yengo, Raymond K.; Johansson, Renzo; Thorvaldsen, Hege O.; Ferreira, Glória C.; Hansson, Mats; Al-Karadaghi, Salam

doi:10.1016/j.jmb.2008.03.040

Cited by 60 publications

(66 citation statements)

References 46 publications

(57 reference statements)

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“…Reduction of ferric iron to ferrous iron may be necessary because iron (III) is very difficult to be released from a tetrapyrrole ring. In addition, the tetrapyrrole ring could be distorted during the enzymatic reaction because it happens during the process of metal insertion catalyzed by ferrochelatase (50).…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure and Biochemical Features of EfeB/YcdB from Escherichia coli O157

Wang

et al. 2011

Journal of Biological Chemistry

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EfeB/YcdB is a member of the dye-decolorizing peroxidase (DyP) protein family. A recent study has shown that this protein can extract iron from heme without breaking the tetrapyrrole ring. We report the crystal structure of EfeB from Escherichia coli O157 bound to heme at 1.95 Å resolution. The EfeB monomer contains two domains. The heme molecule is located in a large hydrophobic pocket in the C-terminal domain. A long loop connecting the two domains extensively interacts with the heme, which is a distinctive structural feature of EfeB homologues. A large tunnel formed by this loop and the ␤-sheet of C-terminal domain provides a potential cofactor/substrate binding site. Biochemical data show that the production of protoporphyrin IX (PPIX) is closely related to the peroxidation activity. The mutant D235N keeps nearly the same activity of guaiacol peroxidase as the wild-type protein, whereas the corresponding mutation in the classic DyP protein family completely abolished the peroxidation activity. These results suggest that EfeB is a unique member of the DyP protein family. In addition, dramatically enhanced fluorescence excitation and emission of EfeB-PPIX was observed, implying this protein may be used as a red color fluorescence marker.

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Section: Discussionmentioning

confidence: 99%

Crystal Structure and Biochemical Features of EfeB/YcdB from Escherichia coli O157

Wang

et al. 2011

Journal of Biological Chemistry

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“…Spontaneously, iron is removed from heme by treatment with HCl (24). The enzymatic reaction could involve a distortion of the tetrapyrrol ring, as it is achieved by ferrochelatase during metal insertion (25). However, in the heme-TyrA structure (a YfeX ortholog), the protoporphyrin ring is plane (26).…”

Section: Discussionmentioning

confidence: 99%

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

Létoffé

Heuck

Delepelaire

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

131

126

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Because heme is a major iron-containing molecule in vertebrates, the ability to use heme-bound iron is a determining factor in successful infection by bacterial pathogens. Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli. YfeX is located in the cytoplasm. EfeB is periplasmic and enables iron extraction from heme in the periplasm and iron uptake in the absence of any heme permease. YfeX and EfeB are widespread and highly conserved in bacteria. We propose that their physiological function is to retrieve iron from heme

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“…A number of X-ray crystallographic structures at about a 2-Å resolution have been determined for wild-type and variant forms of B. subtilis CpfC (222)(223)(224)(225)(226)(227). Additionally, structures with the inhibitor N-methylmesoporphyrin (NMMP) and 2,4-disulfonic acid deuteroporphyrin IX (dSDP) (similar to coproporphyrin III but with sulfonate groups replacing the propionate groups of the A and B rings) have been determined.…”

Section: Porphyrin Metalation By Coproporphyrin Ferrochelatase (Cpfc)mentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

260

335

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SUMMARY The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single heme biosynthetic pathway existed in nature, over the past decade, it has become clear that there are three distinct pathways among prokaryotes, although all three pathways utilize a common initial core of three enzymes to produce the intermediate uroporphyrinogen III. The most ancient pathway and the only one found in the Archaea converts siroheme to protoheme via an oxygen-independent four-enzyme-step process. Bacteria utilize the initial core pathway but then add one additional common step to produce coproporphyrinogen III. Following this step, Gram-positive organisms oxidize coproporphyrinogen III to coproporphyrin III, insert iron to make coproheme, and finally decarboxylate coproheme to protoheme, whereas Gram-negative bacteria first decarboxylate coproporphyrinogen III to protoporphyrinogen IX and then oxidize this to protoporphyrin IX prior to metal insertion to make protoheme. In order to adapt to oxygen-deficient conditions, two steps in the bacterial pathways have multiple forms to accommodate oxidative reactions in an anaerobic environment. The regulation of these pathways reflects the diversity of bacterial metabolism. This diversity, along with the late recognition that three pathways exist, has significantly slowed advances in this field such that no single organism's heme synthesis pathway regulation is currently completely characterized.

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Porphyrin Binding and Distortion and Substrate Specificity in the Ferrochelatase Reaction: The Role of Active Site Residues

Cited by 60 publications

References 46 publications

Crystal Structure and Biochemical Features of EfeB/YcdB from Escherichia coli O157

Crystal Structure and Biochemical Features of EfeB/YcdB from Escherichia coli O157

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

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