Open AccessA large conformational change in the putative ATP pyrophosphatase PF0828 induced by ATP binding
Author(s) -
Forouhar Farhad,
Saadat Nabila,
Hussain Munif,
Seetharaman Jayaraman,
Lee Insun,
Janjua Haleema,
Xiao Rong,
Shastry Ritu,
Acton Thomas B.,
Montelione Gaetano T.,
Tong Liang
Publication year - 2011
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309111031447
Subject(s) - pyrococcus furiosus , pyrococcus horikoshii , nucleotide , dimer , structural motif , conformational change , pyrophosphatases , hydrolase , pyrophosphatase , archaea , biochemistry , biology , protein structure , sequence motif , chemistry , stereochemistry , enzyme , gene , organic chemistry
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) x E(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.