Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase
Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase
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辅脂肪酶结构及其与胰脂肪酶相互作用的晶体学研究
DOI：
10.1002/pro.5560040107
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发表时间：
1995
期刊：
影响因子：
8
通讯作者：
H. Tilbeurgh
中科院分区：
文献类型：
--
作者：
M. Egloff;L. Sarda;R. Verger;C. Cambillau;H. Tilbeurgh
辅脂酶（Mr 10 kDa）在生理条件（高胆盐浓度）下赋予胰脂肪酶催化活性。先前确定的脂肪酶-辅脂酶复合物的3-X-射线分辨率结构已经表明，在不存在底物的情况下，辅脂酶结合到胰脂肪酶的非催化C-末端结构域（货车Tilbeurgh H，Sarda L，Verger R，Cambillau C，1992，Nature 559：159-162;货车Tilbeurgh等人，1993 a，Nature 362：814-820）。在脂质结合时，胰脂肪酶活性位点的构象变化使表面环（盖）与辅脂酶接触，为该辅因子产生第二个结合位点。通过膦酸盐抑制剂共价抑制胰脂肪酶产生脂肪酶-辅脂酶复合物的更好衍射晶体。从该复合物的2.4-X-分辨率结构，我们给出了辅脂酶的准确描述。它证实了先前提出的二硫键连接（货车Tilbeurgh H，Sarda L，Verger R，Cambillau C，1992，Nature 359：159-162;货车Tilbeurgh等人，1993 a，Nature 362：814-820），其与生物化学分配不一致（Chaillan C，Kerfeldom B，Foglizzo E，Chapus C，1992，Biochem Biophys Res Commun 184：206-211）。辅脂酶缺乏明确的二级结构元件。这种小蛋白似乎主要通过五个二硫键的延伸网络来稳定，该网络贯穿扁平形状的分子，网状其四个指状环。辅脂酶表面可以分为一个相当亲水的部分，与脂肪酶相互作用，和一个更疏水的部分，由指尖形成。辅脂酶和脂肪酶C末端结构域之间的相互作用通过8个氢键和大约80个货车范德华接触来稳定。在打开盖子时，增加了三个氢键和大约28个货车范德华接触，解释了在脂质/水界面存在下较高的表观亲和力。指状物的尖端是非常移动的并且构成脂质相互作用表面。在晶体中观察到两个与辅脂酶相互作用的洗涤剂分子，覆盖部分疏水表面。
Colipase (Mr 10 kDa) confers catalytic activity to pancreatic lipase under physiological conditions (high bile salt concentrations). Previously determined 3‐Å‐resolution X‐ray structures of lipase‐colipase complexes have shown that, in the absence of substrate, colipase binds to the noncatalytic C‐terminal domain of pancreatic lipase (van Tilbeurgh H, Sarda L, Verger R, Cambillau C, 1992, Nature 559:159–162; van Tilbeurgh et al., 1993a, Nature 362:814–820). Upon lipid binding, conformational changes at the active site of pancreatic lipase bring a surface loop (the lid) in contact with colipase, creating a second binding site for this cofactor. Covalent inhibition of the pancreatic lipase by a phosphonate inhibitor yields better diffracting crystals of the lipase‐colipase complex. From the 2.4‐Å‐resolution structure of this complex, we give an accurate description of the colipase. It confirms the previous proposed disulfide connections (van Tilbeurgh H, Sarda L, Verger R, Cambillau C, 1992, Nature 359:159–162; van Tilbeurgh et al., 1993a, Nature 362:814–820) that were in disagreement with the biochemical assignment (Chaillan C, Kerfelec B, Foglizzo E, Chapus C, 1992, Biochem Biophys Res Commun 184:206–211). Colipase lacks well‐defined secondary structure elements. This small protein seems to be stabilized mainly by an extended network of five disulfide bridges that runs throughout the flatly shaped molecule, reticulating its four finger‐like loops. The colipase surface can be divided into a rather hydrophilic part, interacting with lipase, and a more hydrophobic part, formed by the tips of the fingers. The interaction between colipase and the C‐terminal domain of lipase is stabilized by eight hydrogen bonds and about 80 van der Waals contacts. Upon opening of the lid, three more hydrogen bonds and about 28 van der Waals contacts are added, explaining the higher apparent affinity in the presence of a lipid/water interface. The tips of the fingers are very mobile and constitute the lipid interaction surface. Two detergent molecules that interact with colipase were observed in the crystal, covering part of the hydrophobic surface.
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影响因子：
5.6
作者：
RYDEL, TJ;TULINSKY, A;HUBER, R
通讯作者：
HUBER, R
影响因子：
56.9
作者：
ADLER, M;LAZARUS, RA;WAGNER, G
通讯作者：
WAGNER, G
胆汁盐与猪辅脂肪酶 A 相互作用的 360 MHz 核磁共振和激光光化学诱导动态核极化研究。
DOI：
10.1111/j.1432-1033.1981.tb06181.x
发表时间：
1981
期刊：
European journal of biochemistry
影响因子：
--
作者：
Cozzone,PJ;Canioni,P;Sarda,L;Kaptein,R
通讯作者：
Kaptein,R
犬胰腺辅脂肪酶基因的结构包括启动子区域的两个蛋白质结合位点。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fukuoka,S;Zhang,DE;Taniguchi,Y;Scheele,GA
通讯作者：
Scheele,GA