8QPT

Crystal structure of pyrophosphatase from Ogataea parapolymorpha

Summary for 8QPT

• Entry DOI: 10.2210/pdb8qpt/pdb
• Descriptor: inorganic diphosphatase, GLYCEROL, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: pyrophosphatase, holo-form, hydrolase
• Biological source: Ogataea parapolymorpha
• Total number of polymer chains: 2
• Total formula weight: 65619.47

Authors

Matyuta, I.O.,Rodina, E.V.,Vorobyeva, N.N.,Kurilova, S.A.,Bezpalaya, E.Y.,Boyko, K.M. (deposition date: 2023-10-03, release date: 2024-09-04)

Primary citation

Bezpalaya, E.Y.,Matyuta, I.O.,Vorobyeva, N.N.,Kurilova, S.A.,Oreshkov, S.D.,Minyaev, M.E.,Boyko, K.M.,Rodina, E.V.
The crystal structure of yeast mitochondrial type pyrophosphatase provides a model to study pathological mutations in its human ortholog.
Biochem.Biophys.Res.Commun., 738:150563-150563, 2024

PubMed Abstract: Mutations in human ppa2 gene encoding mitochondrial inorganic pyrophosphatase (PPA2) result in the mitochondria malfunction in heart and brain and lead to early death. In comparison with its cytosolic counterpart, PPA2 of any species is a poorly characterized enzyme with a previously unknown 3D structure. We report here the crystal structure of PPA2 from yeast Ogataea parapolymorpha (OpPPA2), as well as its biochemical characterization. OpPPA2 is a dimer, demonstrating the fold typical for other eukaryotic Family I pyrophosphatases, including the human cytosolic enzyme. Cofactor Mg ions found in OpPPA2 structure have similar coordination to most known Family I pyrophosphatases. Most of the residues associated with the pathological mutations in human PPA2 are conserved in OpPPA2, and their structural context suggests possible explanations for the effects of the mutations on the human enzyme. In this work, the mutant variant of OpPPA2, Met52Val, corresponding to the natural pathogenic variant Met94Val of human PPA2, is characterized. The obtained structural and biochemical data provide a step to understanding the structural basis of PPA2-associated pathologies.

PubMed: 39178581
DOI: 10.1016/j.bbrc.2024.150563

Experimental method

X-RAY DIFFRACTION (1.8 Å)