van Tilbeurgh H, Sarda L, Verger R, Cambillau C
LCCMB-CNRS, Faculté de Médecine Nord, Marseille, France.
Nature. 1992 Sep 10;359(6391):159-62. doi: 10.1038/359159a0.
Interfacial adsorption of pancreatic lipase is strongly dependent on the physical chemical properties of the lipid surface. These properties are affected by amphiphiles such as phospholipids and bile salts. In the presence of such amphiphiles, lipase binding to the interface requires a protein cofactor, colipase. We obtained crystals of the pancreatic lipase-procolipase complex and solved the structure at 3.04 A resolution. Here we describe the structure of procolipase, which essentially consists of three 'fingers' and is topologically comparable to snake toxins. The tips of the fingers contain most of the hydrophobic amino acids and presumably form the interfacial binding site. Lipase binding occurs at the opposite side to this site and involves polar interactions. Determination of the three-dimensional structure of pancreatic lipase has revealed the presence of two domains: an amino-terminal domain, at residues 1-336 containing the active site and a carboxy-terminal domain at residues 337-449 (ref. 6). Procolipase binds exclusively to the C-terminal domain of lipase. No conformational change in the lipase molecule is induced by the binding of procolipase.
胰腺脂肪酶的界面吸附强烈依赖于脂质表面的物理化学性质。这些性质会受到两亲分子如磷脂和胆汁盐的影响。在存在此类两亲分子的情况下，脂肪酶与界面的结合需要一种蛋白质辅因子——辅脂酶。我们获得了胰腺脂肪酶 - 辅脂酶复合物的晶体，并以3.04埃的分辨率解析了其结构。在此我们描述辅脂酶的结构，它主要由三个“指状结构”组成，在拓扑结构上与蛇毒素类似。指状结构的末端包含大部分疏水氨基酸，推测形成界面结合位点。脂肪酶的结合发生在该位点的相反一侧，涉及极性相互作用。胰腺脂肪酶三维结构的测定揭示了存在两个结构域：一个是位于1 - 336位残基的氨基末端结构域，包含活性位点；另一个是位于337 - 449位残基的羧基末端结构域（参考文献6）。辅脂酶仅与脂肪酶的羧基末端结构域结合。辅脂酶的结合未诱导脂肪酶分子发生构象变化。
