title: The structure and catalytic cycle of a sodium-pumping pyrophosphatase.
abstract: Membrane-integral pyrophosphatases (M-PPases) are crucial for the survival of plants, bacteria, and protozoan parasites. They couple pyrophosphate hydrolysis or synthesis to Na(+) or H(+) pumping. The 2.6-angstrom structure of Thermotoga maritima M-PPase in the resting state reveals a previously unknown solution for ion pumping. The hydrolytic center, 20 angstroms above the membrane, is coupled to the gate formed by the conserved Asp(243), Glu(246), and Lys(707) by an unusual "coupling funnel" of six α helices. Comparison with our 4.0-angstrom resolution structure of the product complex suggests that helix 12 slides down upon substrate binding to open the gate by a simple binding-change mechanism. Below the gate, four helices form the exit channel. Superimposing helices 3 to 6, 9 to 12, and 13 to 16 suggests that M-PPases arose through gene triplication.
authors: Structural Biology and Biophysics Program, Institute of Biotechnology, Post Office Box 65, University of Helsinki, FIN-00014, Finland.
authors: Juho
authors: J
authors: Kellosalo
authors: Tommi
authors: T
authors: Kajander
authors: Konstantin
authors: K
authors: Kogan
authors: Kisun
authors: K
authors: Pokharel
authors: Adrian
authors: A
authors: Goldman
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055162:Biocatalysis; D002118:Calcium / Q000737:chemistry; D020134:Catalytic Domain; D002462:Cell Membrane / Q000201:enzymology; D018360:Crystallography, X-Ray; D011756:Diphosphates / Q000378:metabolism*; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011755:Pyrophosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020124:Thermotoga maritima / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D011756:Diphosphates; D012964:Sodium; D011755:Pyrophosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; D002118:Calcium