Palmitic acid is a common saturated fatty acid with a 16-carbon backbone found in fats and waxes including olive oil, palm oil, as well as in butter, cheese, milk and meat. Product of hydrolysis of Palmitate esters
4 structures(e.g. : 6QGQ, 6QGO, 6QGS... more)(less)6QGQ: Crystal structure of human acyl protein thioesterase APT1 C2S mutant bound to palmitic acid, 6QGO: Crystal structure of human acyl protein thioesterase APT1 S119A mutant bound to palmitic acid, 6QGS: Crystal structure of human acyl protein thioesterase APT1 bound to palmitic acid, 6OR3: Structure of an Acyl Intermediate of Thermomyces Lanuginosa Lipase With Palmitic Acid in an Orthorhombic Crystal
Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine hydrolase that exhibits relatively broad substrate specificity. It has been implicated in a variety of endogenous cholesterol metabolism pathways including the following apparently disparate reactions: cholesterol ester hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis (FAEES). The structural basis for the ability of hCE1 to perform these catalytic actions involving large substrates and products has remained unclear. Here we present four crystal structures of the hCE1 glycoprotein in complexes with the following endogenous substrates or substrate analogues: Coenzyme A, the fatty acid palmitate, and the bile acids cholate and taurocholate. While the active site of hCE1 was known to be promiscuous and capable of interacting with a variety of chemically distinct ligands, these structures reveal that the enzyme contains two additional ligand-binding sites and that each site also exhibits relatively non-specific ligand-binding properties. Using this multisite promiscuity, hCE1 appears structurally capable of assembling several catalytic events depending, apparently, on the physiological state of the cellular environment. These results expand our understanding of enzyme promiscuity and indicate that, in the case of hCE1, multiple non-specific sites are employed to perform distinct catalytic actions.
Title: The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis Bellizzi JJ, 3rd, Widom J, Kemp C, Lu JY, Das AK, Hofmann SL, Clardy J Ref: Proc Natl Acad Sci U S A, 97:4573, 2000 : PubMed
Mutations in palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme that removes fatty acyl groups from cysteine residues in modified proteins, cause the fatal inherited neurodegenerative disorder infantile neuronal ceroid lipofuscinosis. The accumulation of undigested substrates leads to the formation of neuronal storage bodies that are associated with the clinical symptoms. Less severe forms of PPT1 deficiency have been found recently that are caused by a distinct set of PPT1 mutations, some of which retain a small amount of thioesterase activity. We have determined the crystal structure of PPT1 with and without bound palmitate by using multiwavelength anomalous diffraction phasing. The structure reveals an alpha/beta-hydrolase fold with a catalytic triad composed of Ser115-His289-Asp233 and provides insights into the structural basis for the phenotypes associated with PPT1 mutations.
