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

2001年7月，BBSRC （719/B15474）提供了260万英镑的资金，随后BBSRC （719/ REI20571）提供了19.5万英镑的赠款，西北发展署（N0002170）提供了17万英镑的项目奖励，使2004年在英国建立了具有世界竞争力的蛋白质晶体学（MAD/SAD）设施，并于2004年10月开始全面用户运营。英国结构生物学社区已经利用这条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以及其他一些高影响力的期刊，包括J Mol Biol和J Biol Chem。这些都有助于阐明酶的机制，破译可能有助于致病特性的结构特征，否则关键的维持生命的生物分子，参与内体膜向内出芽产生多泡体的结构机制等。这些研究和其他研究也将在适当时候刊登在影响很大的期刊上，它们利用了本设施的一项或多项特点，这些特点在目标和技术两节中作了详细概述。上述功能将进一步巩固，特别是在长波使用方面，例如，通过低温流使用氦气来最小化空气路径，以及英国首创的PX/XAFS组合功能。现在，机器人阶段在光束线上全面运行，一些体育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）投资的一部分，这个主要设施的持续可用性将确保BBSRC的投资得到适当的回报。在这条经过试验和测试的波束线上获得的经验将与DIAMOND设施的发展直接相关，例如长波相位和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.