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

2001年7月BBSRC(719/B15474)提供了260万GB的资金，随后BBSRC 719/REI20571提供了GB 195K的赠款，西北开发署(N0002170)提供了GB 170K的项目奖励，使英国于2004年在英国建立了具有世界竞争力的蛋白质结晶(MAD/SAD)设施，并于2004年10月开始全面投入使用。英国结构生物界已经使用这条光束线解决了一系列生物学问题，这是令人印象深刻的。在这短时间内出现了几个主要的生物学亮点，包括在细胞，自然，发育细胞，PNAS上的论文，以及其他几个高影响力的期刊，包括J Mol Biol和J Biol Chem。这些研究有助于阐明酶机制，破译可能导致致病的结构特征，其他关键的维持生命的生物分子的性质，参与内体膜向内萌发以产生多囊泡体的结构机制，等等。这些研究和其他研究，也将在适当的时候发表在影响较大的期刊上，它们利用了目标和技术部分详细概述的这一设施的一个或多个特征。上述能力将进一步得到巩固，特别是对于长波用途，例如通过低温气流使用氦将空气路径降至最低，并结合PX/XAFS能力，这是英国首创的组合。现在，机器人舞台已经在光束线上全面运行，一些体育中心开始生产大量蛋白质和晶体，作为BBSRC最近对理性目标结构蛋白质组学(SPORT)投资的一部分，这一主要设施的持续可用将确保BBSRC的投资实现适当的回报。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戴蒙德设施的发展，例如长波相移和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.