?美国Stanford同步加速辐射实验室（SSRL）的科学家最近发现了结核杆菌控制铜代谢的蛋白的基因。铜是生物必不可少的一种元素，但是其含量必须受到严格控制，因为过量的铜会导致细胞死亡。科学家将研究结果发表在明年1月的《Nature Chemical Biology》上，文章说明了细菌是怎样控制铜的含量的，而这可能发现治疗肺结核的新方法。
??这一研究小组由Texas A&M大学的David Giedroc领导，他们发现多种细菌中都有基因CsoR，这能制造和铜结合的蛋白质。Giedroc说：“金属离子例如铜是很多致病生物的弱点，高浓度的这些离子是致命的，但是细胞又需要这些离子保护蛋白质，DNA等。”
??通过这些蛋白质可以保护细菌免受铜离子的伤害，但是产生这些蛋白质的基因以及这些蛋白保护作用的机制之前并不清楚。科学家之前假设产生相关蛋白的基因应该存在于造成肺结核的结合杆菌的基因组中。Wisconsin大学的Adel Talaat发现CsoR是感染小鼠肺结核的细菌基因组的一部分。对DNA的分析使科学家假设编译的相关蛋白能作为“铜离子泵”将这些离子泵出细胞，CsoR是这一过程中的关键。
??利用SSRL的加速器，科学家使用了X射线吸收光谱技术（XAS）分析纯蛋白样品。X射线穿过样品，激发其中铜原子的电子，就能反映样品的化学特性。Giedroc小组能揭示这种蛋白起作用的内部机制。小组的另一名学者James Sacchettini还用X射线结晶学技术分析了整个蛋白质的结构。
英文原文：
SSRL Research Helps Uncover the Secrets of an Age-Old Killer
Scientists working in part at the Stanford Synchrotron Radiation Laboratory (SSRL) have discovered a gene for a protein that regulates the cellular response to copper in the bacterium that causes tuberculosis. Copper is a biologically essential element, but its levels within a cell must be carefully controlled because too much can cause cell death. These findings, reported in the January issue of Nature Chemical Biology, explain how a wide variety of bacteria control copper concentrations within their cells, and this understanding could lead to new treatments for tuberculosis.
The research team, led by David Giedroc of Texas A&M University, discovered the gene that encodes a "Copper-sensitive operon Repressor" (CsoR), which controls the production of copper-binding proteins and is present in many types of bacteria.
"Metal ions like copper are the 'Achilles heel' of tuberculosis bacilli and other pathogenic organisms," said Giedroc. "Too much of these ions inside a cell is deadly, but the cell needs them to break down reactive compounds that would otherwise destroy important proteins, DNA, and lipids within the cell."
Copper ions are prevented from damaging the cell by regulatory proteins that sense the metal and turn on the production of other proteins that help mitigate the deadly effects of copper. However, the gene responsible for turning on these proteins and the mechanism behind how the protein works had not been previously identified in many bacteria.
The researchers hypothesized that the gene that encodes the copper-binding protein must appear somewhere in the genome of Mycobacterium tuberculosis, the pathogen responsible for tuberculosis infections in humans. The University of Wisconsin's Adel Talaat, a co-author on the study, had previously shown that CsoR was part of a cluster of genes active in M. tuberculosis infecting the lungs of mice. Analysis of the DNA sequence of another nearby gene led the researchers to hypothesize that it encoded a protein that acts as a "copper pump" that drives excess copper out of the cell, and that CsoR was the critical regulator of this process.
Using the synchrotron facilities at SSRL and the Canadian Light Source (CLS), the researchers used a technique called x-ray absorption spectroscopy (XAS) on purified samples of the copper-binding protein from Mycobacterium tuberculosis. With the XAS technique, a beam of x-rays is passed through a sample, exciting the electrons in the sample's copper atoms, thereby revealing important clues about sample's chemistry and how its atoms are bonded. Using this and other techniques, Giedroc and his team uncovered the chemical mechanism behind the copper-binding protein in M. tuberculosis and thus how the protein functions.
"It's a fundamental new discovery which might, down the road, lead to new treatments for tuberculosis," said University of Saskatchewan's Graham George, who collaborated with Giedroc's team on the experiment. "The x-ray absorption spectroscopy part of the work was vital to understanding how the CsoR protein binds copper."
Another member of Giedroc's team, James Sacchettini of Texas A&M, employed a commonly used technique called x-ray crystallography to help determine the overall structure of the copper-binding protein. With this technique, protein molecules are grown into crystals and then exposed to a beam of x-rays. By measuring the pattern of x-rays scattered by the sample, researchers can map out the arrangement of the atoms in a molecule and gather clues about its function.
