title: Crystal structure of HPr kinase/phosphatase from Mycoplasma pneumoniae.
abstract: HPr kinase/phosphatase (HPrK/P) modifies serine 46 of histidine-containing protein (HPr), the phosphorylation state of which is the control point of carbon catabolite repression in low G+C Gram-positive bacteria. To understand the structural mechanism by which HPrK/P carries out its dual, competing activities we determined the structure of full length HPrK/P from Mycoplasma pneumoniae (PD8 ID, 1KNX) to 2.5A resolution. The enzyme forms a homo-hexamer with each subunit containing two domains connected by a short loop. The C-terminal domain contains the well-described P-loop (Walker A box) ATP binding motif and takes a fold similar to phosphoenolpyruvate carboxykinase (PEPCK) from Escherichia coli as recently described in other HPrK/P structures. As expected, the C-terminal domain is very similar to the C-terminal fragment of Lactobacillus casei HPrK/P and the C-terminal domain of Staphylococcus xylosus HPrK/P; the N-terminal domain is very similar to the N-terminal domain of S.xylosus HPrK/P. Unexpectedly, the N-terminal domain resembles UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-diaminopimelate ligase (MurE), yet the function of this domain is unclear. We discuss these observations as well as the structural significance of mutations in the P-loop and HPrK/P family sequence motif.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Allen
authors.forename: Katrin
authors.initials: K
authors.lastname: Steinhauer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hillen
authors.forename: Jörg
authors.initials: J
authors.lastname: Stülke
authors.forename: Richard G
authors.initials: RG
authors.lastname: Brennan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009177:Mycoplasma pneumoniae / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D021122:Protein Subunits; D000255:Adenosine Triphosphate; C110847:HPr kinase; D017346:Protein Serine-Threonine Kinases