1khf | pdb_00001khf
PEPCK complex with PEP
Structural highlights
Disease[PCKGC_HUMAN] Defects in PCK1 are the cause of cytosolic phosphoenolpyruvate carboxykinase deficiency (C-PEPCKD) [MIM:261680]. A metabolic disorder resulting from impaired gluconeogenesis. It is a rare disease with less than 10 cases reported in the literature. Clinical characteristics include hypotonia, hepatomegaly, failure to thrive, lactic acidosis and hypoglycemia. Autoposy reveals fatty infiltration of both the liver and kidneys. The disorder is transmitted as an autosomal recessive trait. Function[PCKGC_HUMAN] Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe report crystal structures of the human enzyme phosphoenolpyruvate carboxykinase (PEPCK) with and without bound substrates. These structures are the first to be determined for a GTP-dependent PEPCK, and provide the first view of a novel GTP-binding site unique to the GTP-dependent PEPCK family. Three phenylalanine residues form the walls of the guanine-binding pocket on the enzyme's surface and, most surprisingly, one of the phenylalanine side-chains contributes to the enzyme's specificity for GTP. PEPCK catalyzes the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Because the gluconeogenic pathway contributes to the fasting hyperglycemia of type II diabetes, inhibitors of PEPCK may be useful in the treatment of diabetes. Crystal structure of human cytosolic phosphoenolpyruvate carboxykinase reveals a new GTP-binding site.,Dunten P, Belunis C, Crowther R, Hollfelder K, Kammlott U, Levin W, Michel H, Ramsey GB, Swain A, Weber D, Wertheimer SJ J Mol Biol. 2002 Feb 15;316(2):257-64. PMID:11851336[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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