Crystal Structure of Pyrococcus furiosus Phosphoglucose Isomerase

Berrisford, John M.; Akerboom, Jasper; Turnbull, A.P.; Geus, Daniel de; Sedelnikova, Svetlana E.; Staton, Ian; McLeod, Cameron W.; Verhees, Corné H.; Oost, John van der; Rice, David W.; Baker, Patrick J.

doi:10.1074/jbc.m305170200

Cited by 34 publications

(30 citation statements)

References 34 publications

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“…Structure Description-The fold of PfPGI has been described previously (4). Briefly, the structure is dominated by the cupin domain, which is a sandwich of two ␤ sheets ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This is markedly smaller than conventional PGI; for instance, the enzyme from P. furiosus comprises a dimer of 43 kDa (1,2), whereas mammalian PGI is a 132-kDa dimer. Based on sequence alignments, it has been suggested that the novel type of PGI contains a cupin fold (2), and this has been confirmed by a recent crystal structure of the enzyme from Pyrococcus furiosus (4). The hallmark of this fold is a ␤ barrel-like structure that frequently, but not exclusively, contains a metal-binding site (for review, see Ref.…”

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confidence: 94%

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Structural Evidence for a Hydride Transfer Mechanism of Catalysis in Phosphoglucose Isomerase from Pyrococcus furiosus

Swan

Solomons²,

Beeson

et al. 2003

Journal of Biological Chemistry

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In the Euryarchaeota species Pyrococcus furiosus and Thermococcus litoralis, phosphoglucose isomerase (PGI) activity is catalyzed by an enzyme unrelated to the well known family of PGI enzymes found in prokaryotes, eukaryotes, and some archaea. We have determined the crystal structure of PGI from Pyrococcus furiosus in native form and in complex with two active site ligands, 5-phosphoarabinonate and gluconate 6-phosphate. In these structures, the metal ion, which in vivo is presumed to be Fe 2؉ , is located in the core of the cupin fold and is immediately adjacent to the C1-C2 region of the ligands, suggesting that Fe 2؉ is involved in catalysis rather than serving a structural role. The active site contains a glutamate residue that contacts the substrate, but, because it is also coordinated to the metal ion, it is highly unlikely to mediate proton transfer in a cis-enediol mechanism. Consequently, we propose a hydride shift mechanism of catalysis. In this mechanism, Fe 2؉ is responsible for proton transfer between O1 and O2, and the hydride shift between C1 and C2 is favored by a markedly hydrophobic environment in the active site. The absence of any obvious enzymatic machinery for catalyzing ring opening of the sugar substrates suggests that pyrococcal PGI has a preference for straight chain substrates and that metabolism in extreme thermophiles may use sugars in both ring and straight chain forms.Phosphoglucose isomerase (PGI) 1 (E.C. 5.3.1.9) catalyzes the interconversion of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which are substrates of glycolysis and gluconeogenesis. The enzyme is represented by two evolutionarily distinct protein families. In eubacteria, eukaryotes, and a few archaea, the enzyme is of the conventional type that has been studied extensively at the biochemical and structural level. To date, the second, novel type has been found in two Euryarchaeota species, Pyrococcus furiosus and Thermococcus litoralis (1-3). This is markedly smaller than conventional PGI; for instance, the enzyme from P. furiosus comprises a dimer of 43 kDa (1, 2), whereas mammalian PGI is a 132-kDa dimer. Based on sequence alignments, it has been suggested that the novel type of PGI contains a cupin fold (2), and this has been confirmed by a recent crystal structure of the enzyme from Pyrococcus furiosus (4). The hallmark of this fold is a ␤ barrel-like structure that frequently, but not exclusively, contains a metal-binding site (for review, see Ref. 5). PGI from T. litoralis, which is highly similar to the enzyme from P. furiosus, contains iron with traces of zinc (3).The reaction catalyzed by PGI is an aldose-ketose isomerization in which a hydrogen atom is transferred between the C1 and C2 positions of the substrate. A second hydrogen, in the form of a proton, also moves between the O1 and O2. The carbon-bound hydrogen can move by one of two mechanisms, a hydride shift or a proton transfer via a cis-enediol intermediate (6). In isomerases that contain a metal ion at the catalytic center the mechanis...

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“…Structure Description-The fold of PfPGI has been described previously (4). Briefly, the structure is dominated by the cupin domain, which is a sandwich of two ␤ sheets ( Fig.…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 94%

Structural Evidence for a Hydride Transfer Mechanism of Catalysis in Phosphoglucose Isomerase from Pyrococcus furiosus

Swan

Solomons²,

Beeson

et al. 2003

Journal of Biological Chemistry

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“…Crystal structure analyses of Pyr. furiosus cPGI (PfcPGI) revealed a cupin fold (cupa, Latin for small barrel) basically consisting of two ␤ sheets forming a small barrel, which contains the metal ion as well as the substrate binding site (91,92) (Fig. 4).…”

Section: Figmentioning

confidence: 99%

Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation

Bräsen

Esser

Rauch

et al. 2014

Microbiol Mol Biol Rev

271

294

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SUMMARY The metabolism of Archaea , the third domain of life, resembles in its complexity those of Bacteria and lower Eukarya . However, this metabolic complexity in Archaea is accompanied by the absence of many “classical” pathways, particularly in central carbohydrate metabolism. Instead, Archaea are characterized by the presence of unique, modified variants of classical pathways such as the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway. The pentose phosphate pathway is only partly present (if at all), and pentose degradation also significantly differs from that known for bacterial model organisms. These modifications are accompanied by the invention of “new,” unusual enzymes which cause fundamental consequences for the underlying regulatory principles, and classical allosteric regulation sites well established in Bacteria and Eukarya are lost. The aim of this review is to present the current understanding of central carbohydrate metabolic pathways and their regulation in Archaea . In order to give an overview of their complexity, pathway modifications are discussed with respect to unusual archaeal biocatalysts, their structural and mechanistic characteristics, and their regulatory properties in comparison to their classic counterparts from Bacteria and Eukarya . Furthermore, an overview focusing on hexose metabolic, i.e., glycolytic as well as gluconeogenic, pathways identified in archaeal model organisms is given. Their energy gain is discussed, and new insights into different levels of regulation that have been observed so far, including the transcript and protein levels (e.g., gene regulation, known transcription regulators, and posttranslational modification via reversible protein phosphorylation), are presented.

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“…PGI structures have been solved from a variety of mammalian sources and from B. stearothermophilus in native, inhibitor, and substrate (F6P)-bound forms (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). CD spectra analysis and secondary structure predictions suggest a similar fold of the PGI/PMI from A. pernix and T. acidophilum and e.g.…”

Section: Molecular and Thermophilic Properties-thementioning

confidence: 99%

Bifunctional Phosphoglucose/Phosphomannose Isomerases from the Archaea Aeropyrum pernix and Thermoplasma acidophilum Constitute a Novel Enzyme Family within the Phosphoglucose Isomerase Superfamily

Hansen

Wendorff

Schönheit

2004

Journal of Biological Chemistry

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The hyperthermophilic crenarchaeon Aeropyrum pernix contains phosphoglucose isomerase (PGI) activity. However, obvious homologs with significant identity to known PGIs could not be identified in the sequenced genome of this organism. The PGI activity from A. pernix was purified and characterized. Kinetic analysis revealed that, unlike all known PGIs, the enzyme catalyzed reversible isomerization not only of glucose 6-phosphate but also of epimeric mannose 6-phosphate at similar catalytic efficiency, thus defining the protein as bifunctional phosphoglucose/phosphomannose isomerase (PGI/PMI). The gene pgi/pmi encoding PGI/PMI (open reading frame APE0768) was identified by matrixassisted laser desorption ionization time-of-flight analyses; the gene was overexpressed in Escherichia coli as functional PGI/PMI. Putative PGI/PMI homologs were identified in several (hyper)thermophilic archaea and two bacteria. The homolog from Thermoplasma acidophilum (Ta1419) was overexpressed in E. coli, and the recombinant enzyme was characterized as bifunctional PGI/PMI. PGI/PMIs showed low sequence identity to the PGI superfamily and formed a distinct phylogenetic cluster. However, secondary structure predictions and the presence of several conserved amino acids potentially involved in catalysis indicate some structural and functional similarity to the PGI superfamily. Thus, we propose that bifunctional PGI/PMI constitutes a novel protein family within the PGI superfamily.Phosphoglucose isomerase (PGI 1 ; EC 5.3.1.9) catalyzes the reversible isomerization of glucose 6-phosphate to fructose 6-phosphate. PGI plays a central role in sugar metabolism of eukarya, bacteria, and Archaea both in glycolysis via the Embden-Meyerhof pathway in eukarya and bacteria and in its modified versions found in Archaea. PGI is also involved in gluconeogenesis where the enzyme operates in the reverse direction (for the literature see Refs. 1-3). PGIs from the domains of eukarya and bacteria are well studied enzymes. A variety of PGIs have been purified and biochemically characterized, and the encoding genes have been cloned and sequenced (e.g. Refs. 4 -11). Crystal structures have been determined for the eukaryotic PGIs from pig, rabbit, human, and from the bacterium Bacillus stearothermophilus, and conserved amino acids proposed to be involved in substrate binding and/or catalysis have been identified (12-15, 17, 18, 20 -25). The eukaryal and bacterial PGIs belong to the PGI superfamily defined by its two conserved signature patternsTo date this superfamily includes more than 300 PGI sequences (see www.sanger.ac.uk/cgi-bin/Pfam/getacc?PF00342) (26) from bacteria and eukarya but only three from the archaeal domain. These include the PGI from the hyperthermophilic euryarchaeon Methanococcus jannaschii (MjPGI). This PGI has recently been characterized as the first archaeal member of the PGI superfamily. 2 So far little is known about other archaeal PGIs. Recently, two other euryarchaeal PGIs have been characterized, one from the hyperthermophilic euryarch...

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Crystal Structure of Pyrococcus furiosus Phosphoglucose Isomerase

Cited by 34 publications

References 34 publications

Structural Evidence for a Hydride Transfer Mechanism of Catalysis in Phosphoglucose Isomerase from Pyrococcus furiosus

Structural Evidence for a Hydride Transfer Mechanism of Catalysis in Phosphoglucose Isomerase from Pyrococcus furiosus

Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation

Bifunctional Phosphoglucose/Phosphomannose Isomerases from the Archaea Aeropyrum pernix and Thermoplasma acidophilum Constitute a Novel Enzyme Family within the Phosphoglucose Isomerase Superfamily

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