Crystal structure of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase

Mammalian pyruvate dehydrogenase (PDH) activity is tightly regulated by phosphorylation and dephosphorylation, which is catalyzed by PDH kinase isomers and PDH phosphatase isomers, respectively. PDH phosphatase isomer 1 (PDP1) is a heterodimer consisting of a catalytic subunit (PDP1c) and a regulato...

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Published in:Acta crystallographica. Section F, Structural biology communications Structural biology communications, 2020-07, Vol.76 (7), p.292-301
Main Authors: Guo, Youzhong, Qiu, Weihua, Roche, Thomas E., Hackert, Marvin L.
Format: Article
Language:English
Subjects:
cis‐peptide
Crystal structure
Crystallography
Crystals
Dehydrogenase
Dehydrogenases
Dephosphorylation
Ion pairs
Isomers
Kinases
Manganese ions
Molecular structure
Phosphatase
Phosphorylation
pyruvate dehydrogenase
Pyruvate dehydrogenase (lipoamide)
pyruvate dehydrogenase phosphatase
Pyruvic acid
Research Communications
Water chemistry
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Summary:Mammalian pyruvate dehydrogenase (PDH) activity is tightly regulated by phosphorylation and dephosphorylation, which is catalyzed by PDH kinase isomers and PDH phosphatase isomers, respectively. PDH phosphatase isomer 1 (PDP1) is a heterodimer consisting of a catalytic subunit (PDP1c) and a regulatory subunit (PDP1r). Here, the crystal structure of bovine PDP1c determined at 2.1 Å resolution is reported. The crystals belonged to space group P3221, with unit‐cell parameters a = b = 75.3, c = 173.2 Å. The structure was solved by molecular‐replacement methods and refined to a final R factor of 21.9% (Rfree = 24.7%). The final model consists of 402 of a possible 467 amino‐acid residues of the PDP1c monomer, two Mn2+ ions in the active site, an additional Mn2+ ion coordinated by His410 and His414, two MnSO4 ion pairs at special positions near the crystallographic twofold symmetry axis and 226 water molecules. Several new features of the PDP1c structure are revealed. The requirements are described and plausible bases are deduced for the interaction of PDP1c with PDP1r and other components of the pyruvate dehydrogenase complex. The crystal structure of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase provides new insights into the mechanism of the regulation of the activity of the pyruvate dehydrogenase complex.
ISSN:2053-230X
2053-230X
DOI:10.1107/S2053230X20007943