Tracking the Evolution of Porphobilinogen Synthase Metal Dependence in Vitro

Frere, F.; Reents, Heike; Schubert, Wolf‐Dieter; Heinz, Dirk W.; Jahn, Dieter

doi:10.1016/j.jmb.2004.10.053

Cited by 15 publications

(9 citation statements)

References 27 publications

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“…Unlike the P. aeruginosa enzyme, E. coli PbgS is symmetric. Interestingly, crystal structures of P. aeruginosa variants with cysteine substitutions show decreasing asymmetry with increasing numbers of cysteines (97).…”

Section: The Tetrapyrrole Biosynthesis Pathway Common Core 5-aminolevmentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

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273

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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Section: The Tetrapyrrole Biosynthesis Pathway Common Core 5-aminolevmentioning

confidence: 99%

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Dailey

Gerdes³

et al. 2017

Microbiol Mol Biol Rev

Self Cite

273

335

View full text Add to dashboard Cite

show abstract

“…32,33 Considerable attention has been given to the evolution of PBGS active site metal specificity, though the phylogenetic rationale for such an evolutionary change remains speculative. 34,35 Studies directed at inserting the cysteine rich metal-binding sequence into a PBGS that does not naturally have this site, or vice versa, have resulted in proteins with altered metal selectivity, but very low activity. 34,35 Once both substrates are bound at the PBGS active site, the carboxyl group of A-side ALA interacts with conserved basic residues on a mobile loop that has been referred to as the active site lid (residues 209-223 of human PBGS).…”

Section: The Pbgs-catalyzed Reactionmentioning

confidence: 99%

“…34,35 Studies directed at inserting the cysteine rich metal-binding sequence into a PBGS that does not naturally have this site, or vice versa, have resulted in proteins with altered metal selectivity, but very low activity. 34,35 Once both substrates are bound at the PBGS active site, the carboxyl group of A-side ALA interacts with conserved basic residues on a mobile loop that has been referred to as the active site lid (residues 209-223 of human PBGS). In the case of zinc-utilizing PBGS, the basic residues are both arginine (Arg 209 and Arg 221 of human PBGS); in PBGS that do not use zinc, one of the residues is replaced by a lysine (in place of the Arg 221 ) (see Figure 2).…”

Section: The Pbgs-catalyzed Reactionmentioning

confidence: 99%

“…5. eight per octamer; unlike the first structure, these later structures all contained active site ligands. 35,51,55,76 The molecular details of the allosteric magnesium binding site show an octahedral first coordination sphere containing five water molecules and the carboxylate group of a glutamic acid residue. Second coordination sphere ligands and structural details within the context of PBGS assembly are discussed below.…”

Section: The Allosteric Magnesium Ionmentioning

confidence: 99%

“…59 The hugging dimer is the asymmetric crystallographic unit in many PBGS crystal structures. 7,27,35,51,52,55,75,[81][82][83] As shown in Figure 10A, the hugging dimer assembly includes interactions between the C-terminal edge of the active site lid and the N-terminal arm of the neighboring subunit. Amino acids that comprise this interaction are phylogenetically variable.…”

Section: A Intersubunit Interactions In Pbgs Multimersmentioning

confidence: 99%

See 2 more Smart Citations

The Dance of Porphobilinogen Synthase in the Control of Tetrapyrrole Biosynthesis

Jaffe¹,

Lawrence²

2013

Handbook of Porphyrin Science

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The Tetrapyrrole Biosynthetic Pathway and Its Regulation in Rhodobacter capsulatus

Zappa

Bauer

2010

Advances in Experimental Medicine and Biology

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The purple anoxygenic photosynthetic bacterium Rhodobacter capsulatus is capable of growing in aerobic or anaerobic conditions, in the dark or using light, etc. Achieving versatile metabolic adaptations from respiration to photosynthesis requires the use of tetrapyrroles such as heme and bacteriochlorophyll, in order to carry oxygen, to transfer electrons and to harvest light energy. A third tetrapyrrole, cobalamin (vitamin B12), is synthesized and used as a cofactor for many enzymes. Heme, bacteriochlorophyll and vitamin B12 constitute three major end products of the tetrapyrrole biosynthetic pathway in purple bacteria. Their respective synthesis involves a plethora of enzymes several that have been characterized and several that are uncharacterized as described in this review. To respond to changes in metabolic requirements the pathway undergoes complex regulation to direct the flow of tetrapyrrole intermediates into a specific branch(s) at the expense other branches of the pathway. Transcriptional regulation of the tetrapyrrole synthesizing enzymes by redox conditions and pathway intermediates is reviewed. In addition, we discus the involvement of several transcription factors (RegA, CrtJ, FnrL, AerR, HbrL, Irr) as well as the role of riboswitches. Finally, the interdependence of the tetrapyrrole branches on each others synthesis is discussed.

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Tracking the Evolution of Porphobilinogen Synthase Metal Dependence in Vitro

Cited by 15 publications

References 27 publications

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

The Dance of Porphobilinogen Synthase in the Control of Tetrapyrrole Biosynthesis

The Tetrapyrrole Biosynthetic Pathway and Its Regulation in Rhodobacter capsulatus

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