Structure of the Full-Length HPr Kinase/Phosphatase from Staphylococcus xylosus at 1.95 Å Resolution: Mimicking the Product/Substrate of the Phospho Transfer Reactions

The histidine containing phospho carrier protein (HPr) kinase/phosphatase is involved in carbon catabolite repression, mainly in Gram-positive bacteria. It is a bifunctional enzyme that phosphorylates Ser-46-HPr in an ATP-dependent reaction and dephosphorylates P-Ser-46-HPr. X-ray analysis of the fu...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2002-03, Vol.99 (6), p.3458-3463
Hauptverfasser: Márquez, José Antonio, Hasenbein, Sonja, Koch, Brigitte, Fieulaine, Sonia, Nessler, Sylvie, Russell, Robert B., Hengstenberg, Wolfgang, Scheffzek, Klaus
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container_issue 6
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container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 99
creator Márquez, José Antonio
Hasenbein, Sonja
Koch, Brigitte
Fieulaine, Sonia
Nessler, Sylvie
Russell, Robert B.
Hengstenberg, Wolfgang
Scheffzek, Klaus
description The histidine containing phospho carrier protein (HPr) kinase/phosphatase is involved in carbon catabolite repression, mainly in Gram-positive bacteria. It is a bifunctional enzyme that phosphorylates Ser-46-HPr in an ATP-dependent reaction and dephosphorylates P-Ser-46-HPr. X-ray analysis of the full-length crystalline enzyme from Staphylococcus xylosus at a resolution of 1.95 Å shows the enzyme to consist of two clearly separated domains that are assembled in a hexameric structure resembling a three-bladed propeller. The N-terminal domain has a βαβ fold similar to a segment from enzyme I of the sugar phosphotransferase system and to the uridyl-binding portion of MurF; it is structurally organized in three dimeric modules exposed to form the propeller blades. Two unexpected phosphate ions associated with highly conserved residues were found in the N-terminal dimeric interface. The C-terminal kinase domain is similar to that of the Lactobacillus casei enzyme and is assembled in six copies to form the compact central hub of the propeller. Beyond previously reported similarity with adenylate kinase, we suggest evolutionary relationship with phosphoenolpyruvate carboxykinase. In addition to a phosphate ion in the phosphate-binding loop of the kinase domain, we have identified a second phosphate-binding site that, by comparison with adenylate kinases, we believe accommodates a product/substrate phosphate, normally covalently linked to Ser-46 of HPr. Thus, we propose that our structure represents a product/substrate mimic of the kinase/phosphatase reaction.
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It is a bifunctional enzyme that phosphorylates Ser-46-HPr in an ATP-dependent reaction and dephosphorylates P-Ser-46-HPr. X-ray analysis of the full-length crystalline enzyme from Staphylococcus xylosus at a resolution of 1.95 Å shows the enzyme to consist of two clearly separated domains that are assembled in a hexameric structure resembling a three-bladed propeller. The N-terminal domain has a βαβ fold similar to a segment from enzyme I of the sugar phosphotransferase system and to the uridyl-binding portion of MurF; it is structurally organized in three dimeric modules exposed to form the propeller blades. Two unexpected phosphate ions associated with highly conserved residues were found in the N-terminal dimeric interface. The C-terminal kinase domain is similar to that of the Lactobacillus casei enzyme and is assembled in six copies to form the compact central hub of the propeller. Beyond previously reported similarity with adenylate kinase, we suggest evolutionary relationship with phosphoenolpyruvate carboxykinase. In addition to a phosphate ion in the phosphate-binding loop of the kinase domain, we have identified a second phosphate-binding site that, by comparison with adenylate kinases, we believe accommodates a product/substrate phosphate, normally covalently linked to Ser-46 of HPr. Thus, we propose that our structure represents a product/substrate mimic of the kinase/phosphatase reaction.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>11904409</pmid><doi>10.1073/pnas.052461499</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Amino Acid Sequence
Bacterial Proteins
Binding Sites
Biochemistry
Biological Sciences
Crystallization
Crystallography, X-Ray
Crystals
Dimers
Enzymes
Evolution, Molecular
Ions
Models, Molecular
Molecular Mimicry
Molecular Sequence Data
Molecules
Multienzyme Complexes - chemistry
Multienzyme Complexes - metabolism
Phosphates
Phosphates - metabolism
Phosphoprotein Phosphatases - chemistry
Phosphoprotein Phosphatases - metabolism
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Subunits
Protein-Serine-Threonine Kinases - chemistry
Protein-Serine-Threonine Kinases - metabolism
Proteins
Sequence Alignment
Staphylococcus
Staphylococcus - enzymology
title Structure of the Full-Length HPr Kinase/Phosphatase from Staphylococcus xylosus at 1.95 Å Resolution: Mimicking the Product/Substrate of the Phospho Transfer Reactions
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