1m51
From Proteopedia
PEPCK complex with a GTP-competitive inhibitor
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 PubMedThe analysis of the X-ray structures of two xanthine inhibitors bound to PEPCK and a comparison to the X-ray structure of GTP bound to PEPCK are reported. The SAR at N-1, N-7 and developing SAR at C-8 are consistent with information gained from the X-ray structures of compounds 1 and 2 bound to PEPCK. Representative N-3 modifications of compound 2 that led to the discovery of 3-cyclopropylmethyl and its carboxy analogue as optimal N-3 groups are presented. X-ray structures of two xanthine inhibitors bound to PEPCK and N-3 modifications of substituted 1,8-dibenzylxanthines.,Foley LH, Wang P, Dunten P, Ramsey G, Gubler ML, Wertheimer SJ Bioorg Med Chem Lett. 2003 Nov 3;13(21):3871-4. PMID:14552798[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Dunten, P | Foley, L H | Wang, P | Wertheimer, S J | Gluconeogenesis | Inhibitor | Lyase | Xanthine
