一組由多所研究機構(gòu)組成的課題小組首次成功地對海棲熱袍菌(T. maritima)的蛋白質(zhì)三維結(jié)構(gòu)和主要代謝網(wǎng)絡(luò)建立了一個完整的模型,。對該模型的分析表明,著重強調(diào)一少部分的重要蛋白質(zhì)的結(jié)構(gòu),,將加深對蛋白質(zhì)網(wǎng)絡(luò)的演變以及該蛋白質(zhì)網(wǎng)絡(luò)的功能的了解,。這些研究報告發(fā)表在9月18日的Science雜志上,。
該課題組結(jié)合了生物化學研究,結(jié)構(gòu)基因組學和計算機模型等學科知識,,成功破譯了海棲熱袍菌的主要代謝過程中478個蛋白質(zhì)的形狀,,功能以及這些蛋白之間的相互作用。而且,,研究人員還發(fā)現(xiàn)了這些蛋白質(zhì)以及562種細胞內(nèi)代謝反應(yīng)和83種細胞外代謝反應(yīng)之間的聯(lián)系,。
此外,令研究人員感到驚奇的是,,該網(wǎng)絡(luò)結(jié)構(gòu)中蛋白質(zhì)的保守程度——在478種蛋白質(zhì)的714個結(jié)構(gòu)域中,,僅有182種不同的折疊方式,該發(fā)現(xiàn)驗證了,,自然界可以利用已存在的形狀,,略加修改后可以應(yīng)用于新的任務(wù)中的假說。
利用這些數(shù)據(jù),,科學家在生化和分子水平上同時模擬這些代謝反應(yīng),。而且,,該研究中所建立的各種網(wǎng)絡(luò)關(guān)系還可以應(yīng)用到其他許多生物的研究中,包括人類研究,。(生物谷Bioon.com)
生物谷推薦原始出處:
Science 18 September 2009:DOI: 10.1126/science.1174671
Three-Dimensional Structural View of the Central Metabolic Network of Thermotoga maritima
Ying Zhang,1,* Ines Thiele,2,*, Dana Weekes,3 Zhanwen Li,1 Lukasz Jaroszewski,3 Krzysztof Ginalski,4 Ashley M. Deacon,5 John Wooley,6 Scott A. Lesley,7 Ian A. Wilson,8 Bernhard Palsson,2 Andrei Osterman,9 Adam Godzik1,3,6,
Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of these folds are already present in the essential core (~30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks.
1 Joint Center for Molecular Modeling (JCMM), Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
2 Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093–0412, USA.
3 Joint Center for Structural Genomics (JCSG), Bioinformatics Core, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
4 Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Warsaw, Poland.
5 JCSG, Structure Determination Core, Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.
6 JCSG, Bioinformatics Core, University of California at San Diego, La Jolla, CA 92093, USA.
7 JCSG, Crystallomics Core, Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
8 JCSG, The Scripps Research Institute, La Jolla, CA 92037, USA.
9 Burnham Institute for Medical Research, La Jolla, CA 92037, USA.