Equipment to Support Protein Crystallisation in the York Structural Biology Laboratory

约克结构生物学实验室支持蛋白质结晶的设备

基本信息

  • 批准号:
    BB/E012973/1
  • 负责人:
  • 金额:
    $ 7.93万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2007
  • 资助国家:
    英国
  • 起止时间:
    2007 至 无数据
  • 项目状态:
    已结题

项目摘要

The determination of the structure of biological macromolecules using X-ray crystallography is providing information about how biological systems work at the level of individual molecules. This information has transformed our understanding of some of the fundamental processes of life. One example is the crystal structures of the protein haemoglobin in the presence and absence of oxygen which explain how blood cells are able to transport oxygen from the lungs to the tissues. A second example would be how the activity of metabolic enzymes such as glycogen phosphorylase are regulated so that cells either burn or store food depending on the nutritional state of the organism. In addition, crystal structures of key proteins can give important information about what happens at the molecular level in disease or infection and can guide the development of new drugs. A striking and topical example is the determination of the structure of the enzyme neuraminidase from the influenza virus. The structure was used to direct the development of the drugs relenza and subsequently tamiflu. Moreover, structures of neuraminidase and other influenza proteins allow us to understand why variants of flu (such as avian influenza or the Spanish flu of 1918) are so virulent, perhaps providing guidance on developing even better drugs. There are a number of steps in protein crystallography before a structure can be determined. The process starts with the production of large quantities of the protein of interest. The next, key step is to produce crystals of the protein. This can be a long and difficult process, finding the right solution conditions under which crystals will form. Crystals are necessary as when you shine X-rays on a crystal, you obtain a diffraction pattern from which, with a lot of effort, you can extract an image of what the structure of the molecule looks like. Therefore, the success of X-ray analysis is underpinned and determined by successful provision of crystals. In recent years, there have been continual improvements in both the design of the solution conditions and the robotics equipment available for setting up large numbers of crystallisation trials. A particularly important development has been the use of very small, nano-litre sized drops. These reduce the amount of protein that needs to be used, increases the number of crystallisation trials that can be conducted and in some cases, the small drops have increased the success of forming crystals. The Structural Biology Laboratory at York (YSBL) is one of the largest laboratories in Europe dedicated to the determination and analysis of protein structure. Scientists in YSBL have made major contributions by not only determining the structures of many important proteins, but also in developing the experimental and computational methods that are required for X-ray crystal structure determination. One element of this methods development has been devising new crystallisation screen solutions and also working with the manufacturers in developing improved robotics equipment. This application is for an upgrade to the robotics equipment that supports crystallisation trials in YSBL. This will allow scientists at York to benefit from some of the advances in equipment, to determine the structures of more proteins, more rapidly, but also to continue to work with manufacturers in making further improvements.
使用X射线晶体学确定生物大分子的结构提供了有关生物系统如何在单个分子水平上工作的信息。这些信息改变了我们对生命的一些基本过程的理解。其中一个例子是血红蛋白在有氧和无氧情况下的晶体结构,它解释了血细胞如何能够将氧气从肺输送到组织。第二个例子是代谢酶如糖原磷酸化酶的活性是如何调节的,从而使细胞根据生物体的营养状态来燃烧或储存食物。此外,关键蛋白质的晶体结构可以提供有关疾病或感染中分子水平发生的重要信息,并可以指导新药的开发。一个突出的和局部的例子是确定的结构的酶神经氨酸酶从流感病毒。这种结构被用于指导药物瑞乐沙和随后的达菲的开发。此外,神经氨酸酶和其他流感蛋白的结构使我们能够理解为什么流感的变种(如禽流感或1918年的西班牙流感)如此致命,也许可以为开发更好的药物提供指导。在蛋白质晶体学中,在确定结构之前有许多步骤。该过程从生产大量感兴趣的蛋白质开始。下一步,关键的一步是生产蛋白质的晶体。这可能是一个漫长而困难的过程,找到合适的溶液条件下,晶体将形成。晶体是必要的,因为当你用X射线照射晶体时,你会得到一个衍射图案,通过大量的努力,你可以从中提取分子结构的图像。因此,X射线分析的成功取决于晶体的成功供应。近年来,在溶液条件的设计和可用于建立大量结晶试验的机器人设备方面都有了不断的改进。一个特别重要的发展是使用非常小的、纳升大小的液滴。这些减少了需要使用的蛋白质的量,增加了可以进行的结晶试验的数量,并且在某些情况下,小液滴增加了形成晶体的成功率。约克结构生物学实验室(YSBL)是欧洲最大的致力于蛋白质结构测定和分析的实验室之一。YSBL的科学家不仅通过确定许多重要蛋白质的结构,而且还在开发X射线晶体结构测定所需的实验和计算方法方面做出了重大贡献。该方法开发的一个要素是设计新的结晶筛解决方案,并与制造商合作开发改进的机器人设备。此应用程序是为升级的机器人设备,支持结晶试验在YSBL。这将使约克的科学家们能够从设备的一些进步中受益,更快地确定更多蛋白质的结构,同时也能继续与制造商合作进行进一步的改进。

项目成果

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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Andrzej Brzozowski其他文献

A Case Study of Strategic Group Map Application Used as a Tool for Knowledge Management
作为知识管理工具的战略集团图应用案例研究
  • DOI:
    10.1080/08874417.2015.11645758
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    2.8
  • 作者:
    Michał Pietrzak;Krzysztof Jalosinski;J. Paliszkiewicz;Andrzej Brzozowski
  • 通讯作者:
    Andrzej Brzozowski
Bonding of molecular oxygen to T state human haemoglobin
分子氧与 T 态人血红蛋白的结合
  • DOI:
    10.1038/307074a0
  • 发表时间:
    1984-01-05
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Andrzej Brzozowski;Zygmunt Derewenda;Eleanor Dodson;Guy Dodson;Mieczyslaw Grabowski;Robert Liddington;Tadeusz Skarżyński;David Vallely
  • 通讯作者:
    David Vallely

Andrzej Brzozowski的其他文献

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{{ truncateString('Andrzej Brzozowski', 18)}}的其他基金

Revealing Molecular Bases of Signal Transduction through the Drosophila Insulin Receptor: cryoEM and Functional Studies.
揭示果蝇胰岛素受体信号转导的分子基础:冷冻电镜和功能研究。
  • 批准号:
    BB/W003783/1
  • 财政年份:
    2022
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Research Grant
MICA: A molecular dissection of the interplay between diabetes and cancer: an integrated, multidisciplinary approach. II.
MICA:糖尿病和癌症之间相互作用的分子剖析:一种综合的、多学科的方法。
  • 批准号:
    MR/R009066/1
  • 财政年份:
    2018
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Research Grant
A molecular dissection of the interplay between diabetes and cancer: an integrated, multidisciplinary approach
糖尿病和癌症之间相互作用的分子剖析:综合的多学科方法
  • 批准号:
    MR/K000179/1
  • 财政年份:
    2012
  • 资助金额:
    $ 7.93万
  • 项目类别:
    Research Grant

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