STRUCTURAL DETERMINATION OF IRON CONTAINING PROTEIN BY MAD PHASING: DRUG DESIGN

细胞单胞菌FIMIβ-1，4-葡聚糖酶催化结构域 Cex(cex-cd)在很多方面都是保留的原型 β-1，4-葡聚糖酶，这是最重要的 糖中常见的β-1，4-键的切割和实用 对替代能源行业的兴趣 生物质的各种形式。与Steve Withers博士合作，Tony 沃伦和他在不列颠哥伦比亚大学的同事们，我们有 能够单独和In研究Cex-Cd的X射线结构 在酶的催化机理中与中间体形成络合物。 这导致了对这种蛋白质识别的新的见解 特定的糖类运动。它还帮助解决了 关于这个中间体的性质的争论由来已久 反应：我们提供了强有力的证据支持共价 中级模型。我们还能够识别出特定的 酶和底物之间的接触可能有助于 形成反应的转化态。

Cellulomonas fimi beta -1,4-glycanase Cex The catalytic domain from Cex (cex-cd) is in many ways a prototype for the retaining beta-1,4-glycanase enzymes, which are of fundamental importance in the cleavage of common beta -1,4-linkages in saccharides and of practical interest in the alternate energy source industry in treating common forms of biomass. In collaboration with Drs. Steve Withers, Tony Warren and colleagues at the University of British Columbia, we have been able to study the X-ray structures of cex-cd both alone and in complex with intermediates in the catalytic mechanism of the enzyme. This has led to new insights into the recognition by this protein of specific saccharide moeities. It also helped address the long-standing debate about the nature of the intermediate of this reaction: we provided strong evidence supporting the covalent intermediate model. We have also been able to identify specific contacts between the enzyme and the substrate that may assist in forming the tranition state of the reaction.