Provision of the MAD/XAFS facility for the UK structural biology community

2001年7月，BBSRC提供了260万英镑的资金（719/B15474）和BBSRC 719/REI 20571的19.5万英镑后续赠款）和西北发展署的17万英镑项目奖（N 0002170）使世界上具有竞争力的蛋白质晶体学（MAD/SAD）的建立成为可能。2004年在英国的设施，从2004年10月开始全面用户操作。英国结构生物学界已经使用这种光束线解决了一系列生物学问题，这令人印象深刻。在这短时间内出现了几个主要的生物学亮点，包括Cell，Nature，Development Cell，PNAS和其他几个高影响力期刊（包括J Mol Biol和J Biol Chem）的论文。这些论文有助于阐明酶的机制，破译可能导致疾病的结构特征，这些特征可能是维持生命的关键生物分子的特性，这些研究和其他研究也将在适当的时候出现在高影响力的期刊上，它们利用了该设施的一个或多个特征，如在目标和技术章节中详细概述的那样。上述能力将进一步得到巩固，特别是对于长波长用途，例如通过低温流使用氦气来最大限度地减少空气路径，以及组合的PX/XAFS能力（这是英国首创的组合）。现在，机器人阶段在光束线上全面运行，一些SPoRT中心开始生产大量的蛋白质和晶体，作为BBSRC最近对合理目标结构蛋白质组学（SPoRT）的投资的一部分，这一首要设施的持续可用性将确保BBSRC的投资获得适当的回报。在这条经过试验和测试的光束线上获得的经验将直接关系到钻石公司设施的发展，例如长波长定相和MAD/XAFS组合能力。

A £2.6M funding in July 2001 by BBSRC (719/B15474) and a subsequent grant of £195K from BBSRC 719/REI20571) and a project award of £170K from Northwest Development Agency (N0002170) enabled the establishment of a world competitive Protein Crystallography (MAD/SAD) facility in the UK in 2004 with full user operation starting in October 2004. The range of biological problems, which have already been addressed by the UK structural biology community using this beamline is impressive. Several major biological highlights have emerged in this short time including papers in Cell, Nature, Development Cell, PNAS, and several other high impact journals including J Mol Biol and J Biol Chem. These have contributed towards elucidation of enzyme mechanism, deciphering of structural features which may contribute to the disease causing properties of an otherwise key life-sustaining biological molecule, structural mechanisms involved in inward budding of endosomal membranes to generate multivesicular body, etc. These and other studies, which would likewise appear in high impact journals in due course, have made use of one or more of the features of this facility as outlined in detail under the objective and technical sections. The above capabilities would be further consolidated particularly for the long wavelength use, e.g. minimisation of air path through the use of Helium via the cryostream, and combined PX/XAFS capabilities, a combination pioneered in the UK. Now that the robotic stage is in full operation on the beamline and some of the SPoRT centres are beginning to produce a significant number of proteins and crystals as part of the BBSRC's recent investment on structural proteomics of rational targets (SPoRT), continued availability of this premier facility would ensure that a proper return on BBSRC's investment is realised. The experience gained on this tried and tested beamline would be directly relevant to development of facilities at DIAMOND, e.g. long wavelength phasing and combined MAD/XAFS capability.