title: A large conformational change in the putative ATP pyrophosphatase PF0828 induced by ATP binding.
abstract: ATP pyrophosphatases (ATP PPases) are widely distributed in archaea and eukaryotes. They share an HUP domain at the N-terminus with a conserved PP-motif that interacts with the phosphates of ATP. The PF0828 protein from Pyrococcus furiosus is a member of the ATP PPase superfamily and it also has a 100-residue C-terminal extension that contains a strictly conserved EGG(E/D)xE(T/S) motif, which has been named the EGT-motif. Here, crystal structures of PF0828 alone and in complex with ATP or AMP are reported. The HUP domain contains a central five-stranded β-sheet that is surrounded by four helices, as in other related structures. The C-terminal extension forms a separate domain, named the EGT domain, which makes tight interactions with the HUP domain, bringing the EGT-motif near to the PP-motif and defining the putative active site of PF0828. Both motifs interact with the phosphate groups of ATP. A loop in the HUP domain undergoes a large conformational change to recognize the adenine base of ATP. In solution and in the crystal PF0828 is a dimer formed by the side-by-side arrangement of the HUP domains of the two monomers. The putative active site is located far from the dimer interface.
authors.affiliation: Northeast Structural Genomics Consortium, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Forouhar
authors.forename: Nabila
authors.initials: N
authors.lastname: Saadat
authors.forename: Munif
authors.initials: M
authors.lastname: Hussain
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Seetharaman
authors.forename: Insun
authors.initials: I
authors.lastname: Lee
authors.forename: Haleema
authors.initials: H
authors.lastname: Janjua
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Ritu
authors.initials: R
authors.lastname: Shastry
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Acton
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D020027:Pyrococcus furiosus / Q000201:enzymology*; D011755:Pyrophosphatases / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D000255:Adenosine Triphosphate; D011755:Pyrophosphatases
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