1l1f

Structure of human glutamate dehydrogenase-apo formStructure of human glutamate dehydrogenase-apo form

Structural highlights 1l1f is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1hwx, 1hwy, 1hwz Activity: Glutamate dehydrogenase (NAD(P)(+)), with EC number 1.4.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [DHE3_HUMAN] Defects in GLUD1 are the cause of familial hyperinsulinemic hypoglycemia type 6 (HHF6) [MIM:606762]; also known as hyperinsulinism-hyperammonemia syndrome (HHS). Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. In HHF6 elevated oxidation rate of glutamate to alpha-ketoglutarate stimulates insulin secretion in the pancreatic beta cells, while they impair detoxification of ammonium in the liver. Function [DHE3_HUMAN] May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity). 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 PubMed The structure of human glutamate dehydrogenase (GDH) has been determined in the absence of active site and regulatory ligands. Compared to the structures of bovine GDH that were complexed with coenzyme and substrate, the NAD binding domain is rotated away from the glutamate-binding domain. The electron density of this domain is more disordered the further it is from the pivot helix. Mass spectrometry results suggest that this is likely due to the apo form being more dynamic than the closed form. The antenna undergoes significant conformational changes as the catalytic cleft opens. The ascending helix in the antenna moves in a clockwise manner and the helix in the descending strand contracts in a manner akin to the relaxation of an extended spring. A number of spontaneous mutations in this antenna region cause the hyperinsulinism/hyperammonemia syndrome by decreasing GDH sensitivity to the inhibitor, GTP. Since these residues do not directly contact the bound GTP, the conformational changes in the antenna are apparently crucial to GTP inhibition. In the open conformation, the GTP binding site is distorted such that it can no longer bind GTP. In contrast, ADP binding benefits by the opening of the catalytic cleft since R463 on the pivot helix is pushed into contact distance with the beta-phosphate of ADP. These results support the previous proposal that purines regulate GDH activity by altering the dynamics of the NAD binding domain. Finally, a possible structural mechanism for negative cooperativity is presented. The structure of apo human glutamate dehydrogenase details subunit communication and allostery.,Smith TJ, Schmidt T, Fang J, Wu J, Siuzdak G, Stanley CA J Mol Biol. 2002 May 3;318(3):765-77. PMID:12054821 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutamate dehydrogenase 3D structures

spinqualitylabelsall models 1l1f, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image