between two molecules

A population of bacteria living at the bottom of a lake in California found itself, not long ago, at the center of a scientific controversy

A population of bacteria living at the bottom of a lake in California found itself, not long ago, at the center of a scientific controversy: a group of scientists claimed that these tiny creatures, which live on soil rich in a compound called arsenate - based on the toxic element arsenic, can use this compound as a substitute for phosphate - The phosphorus compound that is essential for all living things. Following the claim, which has since been disproved, another question arose: how do creatures that live in arsenate-rich environments manage to distinguish between it and the correct compound, namely phosphate? An answer to this question was recently obtained in a study led by Prof. Dan Toufik from the Weizmann Institute of Science, which was published in the scientific journal Nature.

From a chemical-physical point of view, the difference between phosphate and arsenate is subtle. And yet, while the former is essential to life, the latter poses a great threat to them. How then do bacteria surrounded by arsenate manage to distinguish between two molecules that are almost identical in size, shape, and chemical properties? To investigate the question, Prof. Toufik, together with post-doctoral researcher Dr. Michael Elias, research student Alon Wallner and laboratory technician Corinna Goldin from the Department of Biological Chemistry, together with colleagues from Zurich, examined the protein responsible for mobilizing the phosphate. The protein, called PBP ( phosphate binding protein), located on the outer membrane of the bacterium, where it captures the phosphate molecules and transports them For the pumps - which put them into the cell.

The team of scientists compared the activity of PBP proteins taken from different types of bacteria: some from intestinal bacteria, which are sensitive to arsenate, and some from bacteria resistant to the substance. They found that while the normal bacteria bound phosphate molecules with an affinity 500 times higher than their harmful arsenate, in the resistant bacteria the ratio jumped 5,000 times. That is, to deal with a toxic environment, the bacteria have developed a selective mechanism that ensures a sufficient supply of phosphate, while at the same time making sure that not a single molecule of arsenate will penetrate. Later, to understand how the PBP protein selects phosphate from arsenate, Dr. Elias created crystals of the protein, bound to each of the molecules. A preliminary test showed that the arsenate binding to the protein was done in the same way as the phosphate binding: both the bound molecules and the protein looked identical.

Dr. Elias hypothesized that the key may be a unique and unusual chemical bond between a hydrogen atom in the PBP protein and the molecule that binds to it. Unfortunately, the conventional methods for deciphering the structure of proteins do not usually reach a degree of resolution that allows such differences to be seen. However, having come this far , the team refused to give up. The scientists were able to push the limits of the technology and reach a separation level of a single angstrom (one-tenth of a millionth of a millimeter) - a separation that allows the hydrogen atom to be identified, and to compare the bond it forms with the two different molecules.

The scientists discovered that although the link, in both cases, occurs within a narrow cleft in the valleys of the protein, the angles of the resulting right-hand bond are different. In the case of the phosphate, an ideal bond was created "according to the book". On the other hand, the arsenate molecule - even though it is only slightly larger, is pushed towards the hydrogen in a way that causes it to bind to it at an unnatural, distorted angle. Prof. Toufik believes that, as a result, a repulsion is created between the arsenate and other atoms in the region of the cleft, and that this repulsion prevents the PBP from binding the arsenate molecules with an affinity that allows it to compete with the phosphate and penetrate the interior of the cell.

The importance of the findings is not only in solving a biological mystery. "Phosphate is an extremely essential element for the existence of a living being, and yet, in many places, it is not found in abundance. For this reason, there is great interest in the question of how organisms manage to absorb it," says Prof. Toufik. "This study is the first to indicate the detection mechanism of the PBP protein in relation to arsenate. Apart from that, the study is a fascinating example of the detection capabilities of proteins, and of the subtle mechanisms that allow them to distinguish between two almost identical molecules."

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