4OX2

I45T cytosolic phosphoenolpyruvate carboxykinase in complex with beta-sulfopyruvate and GTP

4OX2 の概要

• エントリーDOI: 10.2210/pdb4ox2/pdb
• 分子名称: Phosphoenolpyruvate carboxykinase, cytosolic [GTP], MANGANESE (II) ION, GUANOSINE-5'-TRIPHOSPHATE, ... (8 entities in total)
• 機能のキーワード: kinase, gluconeogenesis, lyase
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 141300.11

構造登録者

Holyoak, T. (登録日: 2014-02-04, 公開日: 2014-06-11, 最終更新日: 2023-09-27)

主引用文献

Adams, D.R.,Yuan, H.,Holyoak, T.,Arajs, K.H.,Hakimi, P.,Markello, T.C.,Wolfe, L.A.,Vilboux, T.,Burton, B.K.,Fajardo, K.F.,Grahame, G.,Holloman, C.,Sincan, M.,Smith, A.C.,Wells, G.A.,Huang, Y.,Vega, H.,Snyder, J.P.,Golas, G.A.,Tifft, C.J.,Boerkoel, C.F.,Hanson, R.W.,Traynelis, S.F.,Kerr, D.S.,Gahl, W.A.
Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity.
Mol.Genet.Metab., 113:161-170, 2014

PubMed Abstract: The National Institutes of Health Undiagnosed Diseases Program evaluates patients for whom no diagnosis has been discovered despite a comprehensive diagnostic workup. Failure to diagnose a condition may arise from the mutation of genes previously unassociated with disease. However, we hypothesized that this could also co-occur with multiple genetic disorders. Demonstrating a complex syndrome caused by multiple disorders, we report two siblings manifesting both similar and disparate signs and symptoms. They shared a history of episodes of hypoglycemia and lactic acidosis, but had differing exam findings and developmental courses. Clinical acumen and exome sequencing combined with biochemical and functional studies identified three genetic conditions. One sibling had Smith-Magenis Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de novo mutation in GRIN2B, which resulted in markedly reduced glutamate potency of the encoded receptor. Both siblings had a protein-destabilizing homozygous mutation in PCK1, which encodes the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). In summary, we present the first clinically-characterized mutation of PCK1 and demonstrate that complex medical disorders can represent the co-occurrence of multiple diseases.

PubMed: 24863970
DOI: 10.1016/j.ymgme.2014.04.001

実験手法

X-RAY DIFFRACTION (2 Å)