The X-ray Structure of the Plant like 5-Aminolaevulinic Acid Dehydratase from Chlorobium vibrioforme Complexed with the Inhibitor Laevulinic Acid at 2.6Å Resolution

Coates, Leighton; Beaven, G. D. E.; Erskine, P.T.; Beale, Samuel I.; Avissar, Yael J.; Gill, Raj; Mohammed, Fiyaz; Wood, Steve; Shoolingin‐Jordan, Peter M.; Cooper, J.B.

doi:10.1016/j.jmb.2004.07.007

Cited by 16 publications

(20 citation statements)

References 38 publications

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“…The enzyme is a homooctomer in both eukaryotes and prokaryotes (89)(90)(91)(92)(93) and requires metal for activity (94 (98). This enzyme is also stimulated by the monovalent cation K ϩ (98,99).…”

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

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

273

335

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“…Since these early studies PBGS, PBGD, and UROS proteins were purified from many different eukaryotic and prokaryotic sources and biochemically characterized 76. Crystal structures of PBGS were solved much later for the enzymes from yeast, E. coli and Pseudomonas aeruginosa and Chlorobium vibrioforme with many of them containing inhibitors or reaction intermediates 77–80. Structures for PBGD are available for the E. coli and human proteins 81–83.…”

Section: Structures and Mechanisms Of Heme Biosynthetic Enzymesmentioning

confidence: 99%

Structure and function of enzymes in heme biosynthesis

et al. 2010

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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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“…For most species, the asymmetric unit of the crystal structure is an asymmetric homo-dimer (3, 5, 6, 27). The hexamer and its asymmetric unit, the detached dimer (based on PDB code 1PV8) are shown in two shades of blue.…”

Section: Figures and Tablesmentioning

confidence: 99%

Probing the Oligomeric Assemblies of Pea Porphobilinogen Synthase by Analytical Ultracentrifugation

Kokona

Rigotti²,

Wasson³

et al. 2008

Biochemistry

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The enzyme porphobilinogen synthase (PBGS) can exist in different non-additive homo-oligomeric assemblies and, under appropriate conditions, the distribution of these assemblies can respond to ligands such as metals or substrate. PBGS from most organisms was believed to be octameric until work on a rare allele of human PBGS revealed an alternate hexameric assembly, which is also available to the wild type enzyme at elevated pH. Herein, we establish that the distribution of pea PBGS quaternary structures also contains octamers and hexamers, using both sedimentation velocity and sedimentation equilibrium experiments. We report results in which the octamer dominates under purification conditions and discuss conditions that influence the octamer:hexamer ratio. As predicted by PBGS crystal structures from related organisms, in the absence of magnesium, the octameric assembly is significantly destabilized and the oligomeric distribution is dominated largely by the hexameric assembly. Although the PBGS hexamer-to-octamer oligomeric rearrangement is well document under some conditions, both assemblies are very stable (under AUC conditions) in the timeframe of our ultracentrifuge experiments.The enzyme porphobilinogen synthase (PBGS), also known as 5-aminolevulinic acid dehydratase (ALAD), catalyzes the first common step in the biosynthesis of tetrapyrroles including heme, chlorophyll, vitamin B 12 and cofactor F 430 (1,2). The pea (Pisum sativum) PBGS enzyme has been a useful model system to explore metal ion regulation of enzyme activity (2). It has been proposed that part of the regulatory mechanism for pea PBGS activity involves dynamic control of its oligomeric assembly (3) and Mg 2+ has been implicated in the quaternary structure of PBGS from species such as Escherichia coli, Pseudomonas aeruginosa, and Chlorobium vibrioforme (4-6).The dynamic nature of the quaternary structure of pea PBGS under assay conditions results in a protein concentration dependent specific enzyme activity (2). This unusual kinetic phenomenon was originally interpreted as due to an additive equilibrium of oligomeric assemblies that could include less active dimers and tetramers along with active octamers (2); the octamer was well established from the first crystal structure of PBGS (7). A more recent structural hypothesis ascribes the low activity of pea PBGS to a hexameric state, which is nonadditive relative to the octamer, and analogous to the recently determined crystal structure of † This work was supported by NSF grants MCB-0211754 and MCB-0510625 to R.F. and NIH grants ES003654 (EKJ), AI063324 (EKJ), a hexameric form of human PBGS (3). The interconversion of the human PBGS octamer and hexamer is now well established to proceed via a mechanism of dissociation to a dimeric assembly, conformational change at the level of the dimer, and reassociation to the alternate higher order oligomer (8,9). The interpretation of pea PBGS as assembling to either an octamer or a hexamer, as illustrated in Figure 1, is supported by structural a...

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The X-ray Structure of the Plant like 5-Aminolaevulinic Acid Dehydratase from Chlorobium vibrioforme Complexed with the Inhibitor Laevulinic Acid at 2.6Å Resolution

Cited by 16 publications

References 38 publications

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product

Structure and function of enzymes in heme biosynthesis

Probing the Oligomeric Assemblies of Pea Porphobilinogen Synthase by Analytical Ultracentrifugation

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