Persson B, Bengtsson-Olivecrona G, Enerbäck S, Olivecrona T, Jörnvall H
Department of Chemistry I, Karolinska Institutet, Stockholm, Sweden.
Eur J Biochem. 1989 Jan 15;179(1):39-45. doi: 10.1111/j.1432-1033.1989.tb14518.x.
A structural homology between lipoprotein lipase, pancreatic lipase and hepatic lipase is known and indicates that all three lipases are members of a common protein family. Lipoprotein lipase and pancreatic lipase utilize small protein co-factors, apolipoprotein C-II and co-lipase, respectively, but comparisons reveal no homology between the co-factor molecules. Hence, they do not show the same relationship as their target enzymes. Neither do screenings detect any extensive similarities between lipoprotein lipase, serine hydrolases, or apolipoproteins. Scannings against data bank proteins show that a 105-residue segment of lipoprotein lipases exhibits a 35-40% residue identity with a sub-region of Drosophila vitellogenins. One fifth of the conserved amino acid residues (8 of 40) are glycine, a pattern which is typical of distantly related forms of protein families. This supports a true relationship between large segments of Drosophila vitellogenins and lipases. Physiological and functional aspects of the vitellogenin/lipoprotein lipase similarities are given. The region concerned is entirely within the N-terminal domain of lipoprotein lipase and constitutes the segment where the similarity to hepatic and pancreatic lipases is most pronounced. Within this lipase region a 10-residue putative lipid-binding site exists for which further similarities have been found to the otherwise not closely related lingual/gastric lipases, prokaryotic lipases and lecithin-cholesterol acyltransferase. Another segment in lipoprotein lipase, where the heparin-binding site has been mapped, exhibits a correlation between strength of heparin binding and extent of basic residues among members of the lipase family. It further exhibits weak similarities with the 'Zn-finger' DNA-binding segment of steroid hormone receptors and may indicate convergence in a binding interaction. Thus, a functional subdivision of lipoprotein lipase into different segments can be distinguished.
已知脂蛋白脂肪酶、胰脂肪酶和肝脂肪酶之间存在结构同源性，这表明这三种脂肪酶都是一个共同蛋白质家族的成员。脂蛋白脂肪酶和胰脂肪酶分别利用小蛋白质辅因子，即载脂蛋白C-II和辅脂酶，但比较发现这些辅因子分子之间没有同源性。因此，它们与其靶酶的关系并不相同。同样，筛选也未检测到脂蛋白脂肪酶、丝氨酸水解酶或载脂蛋白之间有任何广泛的相似性。对数据库蛋白质的扫描显示，脂蛋白脂肪酶的一个105个残基的片段与果蝇卵黄生成素的一个亚区域具有35 - 40%的残基同一性。保守氨基酸残基的五分之一（40个中的8个）是甘氨酸，这种模式是蛋白质家族远亲形式的典型特征。这支持了果蝇卵黄生成素的大片段与脂肪酶之间存在真正的关系。文中给出了卵黄生成素/脂蛋白脂肪酶相似性的生理和功能方面。相关区域完全在脂蛋白脂肪酶的N端结构域内，并且是与肝脂肪酶和胰脂肪酶相似性最明显的片段。在这个脂肪酶区域内，存在一个10个残基的假定脂质结合位点，已发现它与原本关系不紧密的舌/胃脂肪酶、原核脂肪酶和卵磷脂胆固醇酰基转移酶还有进一步的相似性。脂蛋白脂肪酶中另一个已定位肝素结合位点的片段，显示出肝素结合强度与脂肪酶家族成员中碱性残基数量之间的相关性。它还与类固醇激素受体的“锌指”DNA结合片段有微弱的相似性，这可能表明在结合相互作用上存在趋同现象。因此，可以区分脂蛋白脂肪酶在功能上的不同细分区域。
