Active site geometry of porcine pancreatic lipase: An interesting switchover from Jones' to Seebach's model

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 3; pp. 305 - 307
• Main Authors: BASAK, Amit, KAKALI RANI RUDRA, HUSSAM MOH'D BDOUR, DASGUPTA, Jyotishman
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 12.02.2001
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Catalytic Domain; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Hydrolases; Lactams - metabolism; Lipase - chemistry; Lipase - metabolism; Models, Molecular; Pancreas - enzymology; Protein Binding; Static Electricity; Stereoisomerism; Structure-Activity Relationship; Substrate Specificity; Swine; Substituent effect; Enantioselectivity; Nitrogen heterocycle; Active site; Furan derivatives; Lactam; Triacylglycerol lipase; Esterases; Oxygen heterocycle; Modeling; Stereoselectivity; Thiophene derivatives; Catalytic site; Pancreas; Acylate; Ungulata; Enzyme; Benzene derivatives; Carboxylic ester hydrolases; Primary alcohol; Pig; Hydrolysis; Vertebrata; Sulfur heterocycle; Mammalia; Animal; Hydrolases; Artiodactyla
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00675-2

Porcine pancreatic lipase (PPL)-catalyzed hydrolysis of cis 3-acetoxyethyl-1,4-diphenyl and cis 3-acetoxyethyl-1-phenyl-4-(2-furyl) beta-lactams 1a and 1b proceeded with opposite stereoselectivity while the corresponding thienyl beta-lactam 1c showed no selectivity at all. An explanation based upon the dominance of hydrophobic and polar pockets in governing the stereoselectivity has been proposed.