Hjorth A, Carrière F, Cudrey C, Wöldike H, Boel E, Lawson D M, Ferrato F, Cambillau C, Dodson G G, Thim L
Novo Nordisk A/S, Copenhagen, Denmark.
Biochemistry. 1993 May 11;32(18):4702-7. doi: 10.1021/bi00069a003.
Typically pancreatic lipases are characterized by the following properties: (1) they are activated by lipid/water interfaces (interfacial activation), (2) they are inhibited by bile salts but reactivated by colipase (a small activator protein), and (3) they do not hydrolyze significantly phospholipids. A cDNA clone encoding a guinea pig pancreatic (phospho)lipase (GPL) has been sequenced and expressed. The enzyme (recombinant as well as native) differs from other pancreatic lipases in that (1) it is not interfacially activated, (2) its activity is unaffected by the presence of bile salts and/or colipase using tributyrin as substrate, and (3) it exhibits equally phospholipase A1 and lipase activities. The amino acid sequence of GPL is highly homologous to that of other known pancreatic lipases, with the exception of a deletion in the so-called lid domain that regulates access to the active centers of other lipases. We propose that this deletion is directly responsible for the anomalous behavior of this enzyme. Thus GPL challenges the classical distinction between lipases, esterases, and phospholipases.
通常，胰腺脂肪酶具有以下特性：（1）它们被脂质/水界面激活（界面激活），（2）它们被胆汁盐抑制，但被辅脂酶（一种小的激活蛋白）重新激活，（3）它们不会显著水解磷脂。一个编码豚鼠胰腺（磷酸）脂肪酶（GPL）的cDNA克隆已被测序并表达。该酶（重组酶以及天然酶）与其他胰腺脂肪酶的不同之处在于：（1）它不被界面激活，（2）以三丁酸甘油酯为底物时，其活性不受胆汁盐和/或辅脂酶存在的影响，（3）它同时表现出磷脂酶A1和脂肪酶活性。GPL的氨基酸序列与其他已知胰腺脂肪酶的序列高度同源，除了在所谓的盖子结构域中有一个缺失，该结构域调节对其他脂肪酶活性中心的 access。我们认为这个缺失直接导致了这种酶的异常行为。因此，GPL对脂肪酶、酯酶和磷脂酶之间的经典区分提出了挑战。
