Crystal Structure of an ADP-dependent Glucokinase from Pyrococcus furiosus: Implications for a Sugar-induced Conformational Change in ADP-dependent Kinase

Ito, Sohei; Fushinobu, Shinya; Jeong, Jong-Jin; Yoshioka, Ichiro; Koga, Shinji; Shoun, Hirofumi; Wakagi, Takayoshi

doi:10.1016/s0022-2836(03)00792-7

Cited by 44 publications

(63 citation statements)

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“…Mutation of Arg-205 in TlGK to alanine resulted in Ͻ0.1% the activity of the wild type enzyme (20). We observed the same effect upon mutation of the corresponding arginine residue in PhPFK (Arg-185) to alanine ( Table 1).…”

Section: Resultssupporting

confidence: 72%

“…1). Mutations of this residue in TlGK resulted in a significant reduction of glucokinase activity (20). Similarly, mutation of the corresponding aspartate in PhPFK (Asp-433) to alanine resulted in a loss of PFK activity (Table 1).…”

Section: Resultsmentioning

confidence: 95%

“…In this respect, it has been proposed that the presence of a bulky side chain in the bottom of the nucleotide binding crevice (Tyr-357 in the case of T. litoralis ADP-GK), below the sugar part of the molecule, could account for the change in specificity (20). Moreover, it was proposed that because ADPPFKs have leucine or isoleucine in this position they can marginally use ATP as phosphoryl donor as it was seen for the enzyme from P. furiosus (7).…”

Section: Resultsmentioning

confidence: 99%

“…5) (20,(32)(33)(34)(35). The flexible loops located between the large and small domains form a hinge that folds, closing the cleft between the two domains upon substrate binding (20,(32)(33)(34)(35). This conformational change appears to be essential for positioning the catalytic residues of ADP-GKs and ribokinases (20,34).…”

Section: Resultsmentioning

confidence: 99%

“…Residues responsible for glucose binding are found on the surface of both the large and small domains adjacent to the ADP-binding pocket (19 -21). Upon glucose binding, the protein undergoes a conformational change whereby the large and small domains close in creating the active-site pocket (20). Interestingly, the unique ADP binding pocket of ADP-GKs recognizes the ␣-and ␤-phosphate of the ADP in an almost identical manner to how the ␤-and ␥-phosphate of ATP are recognized in ATP-dependent kinases of the ribokinase superfamily (19).…”

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confidence: 99%

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ADP-dependent 6-Phosphofructokinase from Pyrococcus horikoshii OT3

Currie

Merino

Skarina

et al. 2009

Journal of Biological Chemistry

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Some hyperthermophilic archaea use a modified glycolytic pathway that employs an ADP-dependent glucokinase (ADP-GK) and an ADP-dependent phosphofructokinase (ADP-PFK) or, in the case of Methanococcus jannaschii, a bifunctional ADPdependent glucophosphofructokinase (ADP-GK/PFK). The crystal structures of three ADP-GKs have been determined. However, there is no structural information available for ADPPFKs or the ADP-GK/PFK. Here, we present the first crystal structure of an ADP-PFK from Pyrococcus horikoshii OT3 (PhPFK) in both apo-and AMP-bound forms determined to 2.0-Å and 1.9-Å resolution, respectively, along with biochemical characterization of the enzyme. The overall structure of PhPFK maintains a similar large and small ␣/␤ domain structure seen in the ADP-GK structures. A large conformational change accompanies binding of phosphoryl donor, acceptor, or both, in all members of the ribokinase superfamily characterized thus far, which is believed to be critical to enzyme function. Surprisingly, no such conformational change was observed in the AMPbound PhPFK structure compared with the apo structure. Through comprehensive site-directed mutagenesis of the substrate binding pocket we identified residues that were critical for both substrate recognition and the phosphotransfer reaction. The catalytic residues and many of the substrate binding residues are conserved between PhPFK and ADP-GKs; however, four key residues differ in the sugar-binding pocket, which we have shown determine the sugar-binding specificity. Using these results we were able to engineer a mutant PhPFK that mimics the ADP-GK/PFK and is able to phosphorylate both fructose 6-phosphate and glucose.

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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ADP-dependent 6-Phosphofructokinase from Pyrococcus horikoshii OT3

Currie

Merino

Skarina

et al. 2009

Journal of Biological Chemistry

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Mechanistic Implications of Escherichia coli Galactokinase Structure‐Based Engineering

Hoffmeister

Thorson

2004

ChemBioChem

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The ADP‐dependent sugar kinase family: Kinetic and evolutionary aspects

Guixé

Merino

2009

IUBMB Life

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SummarySome archaea of the Euryarchaeota present a unique version of the Embden-Meyerhof pathway where glucose and fructose-6-phosphate are phoshporylated using ADP instead of ATP as the phosphoryl donor. These are the only ADP-dependent kinases known to date. Although initially they were believed to represent a new protein family, they can be classified as members of the ribokinase superfamily, which also include several ATP-dependent kinases. As they were first identified in members of the thermococcales it was proposed that the presence of these ADP-dependent kinases is an adaptation to high temperatures. Later, homologs of these enzymes were identified in the genomes of mesophilic and thermophilic methanogenic archaea and even in the genomes of higher eukaryotes, suggesting that the presence of these proteins is not related to the hyperthermophilic life. The ADP-dependent kinases are very restrictive to their ligands being unable to use triphosphorylated nucleotides such as ATP. However, it has been shown that they can bind ATP by competition kinetic experiments. The hyperthermophilic methanogenic archaeon Methanocaldococcus jannaschii has a homolog of these genes, which can phosphorylate glucose and fructose-6-phosphate. For this reason, it was proposed as an ancestral form for the family. However, recent studies have shown that the ancestral activity in the group is glucokinase, and a combination of gene duplication and lateral gene transfer could have originated the two paralogs in this member of the Euryarchaeota. Interestingly, based on structural comparisons made within the superfamily it has been suggested that the ADP-dependent kinases are the newest in the group. In several members of the superfamily, the presence of divalent metal cations has been shown to be crucial for catalysis, so its role in the ADP-dependent family was investigated through molecular dynamics. The simulation shows that, in fact, the metal coordinates the catalytic ensemble and interacts with crucial residues for catalysis. Keywords ADP-dependent kinase family; ribokinase superfamily; modified Embden-Meyerhof pathway; glucokinase; phosphofructokinase.Abbreviations ADP-GK, ADP-dependent glucokinase; ADP-PFK, ADP-dependent phosphofructokinase; ThzK, 4-Methyl-5-b-hydroxyethylthiazole kinase; HmppK, 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase.

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Crystal Structure of an ADP-dependent Glucokinase from Pyrococcus furiosus: Implications for a Sugar-induced Conformational Change in ADP-dependent Kinase

Cited by 44 publications

References 50 publications

ADP-dependent 6-Phosphofructokinase from Pyrococcus horikoshii OT3

ADP-dependent 6-Phosphofructokinase from Pyrococcus horikoshii OT3

Mechanistic Implications of Escherichia coli Galactokinase Structure‐Based Engineering

The ADP‐dependent sugar kinase family: Kinetic and evolutionary aspects

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