(Press-News.org) Not long ago, some unassuming bacteria found themselves at the center of a scientific controversy: A group claimed that these microorganisms, which live in an environment that is rich in the arsenic-based compound arsenate, could take up that arsenate and use it – instead of the phosphate that all known life on Earth depends on. The claim, since disproved, raised another question: How do organisms living with arsenate pick and choose the right substance?
Chemically, arsenate is nearly indistinguishable from phosphate. Prof. Dan Tawfik of the Biological Chemistry Department says: "Phosphate forms highly stable bonds in DNA and other key biological compounds, while bonds to arsenate are quickly broken. But how does a microorganism surrounded by arsenate distinguish between two molecules that are almost the same size and have identical shapes and ionic properties?"
To investigate, Tawfik, postdoctoral fellow Dr. Mikael Elias, Ph.D. student Alon Wellner and lab assistant Korina Goldin, in collaboration with Tobias Erb and Julia Vorholt of ETH Zurich, looked at a protein in bacteria that takes up phosphate. This protein, called PBP (short for phosphate binding protein), sits near the bacteria's outer membrane, where it latches onto phosphates and passes them on to pumps that transport them into the cell.
In research that recently appeared in Nature, the team compared the activity of several different PBPs – some from bacteria like E. coli that are sensitive to arsenate and others, like those from the arsenic-rich environment, which are tolerant of the chemical. While the PBPs in the ordinary bacterium were about 500 times more likely to bind phosphate over arsenate, in the arsenic-tolerant bacterium that factor jumped to around 5000. In other words, to cope with their toxic environment, the bacteria evolved a mechanism of extreme selectivity to ensure their supply of phosphate while keeping the arsenate out.
Elias then compared phosphate and arsenate binding by crystallizing PBPs along with one of the two compounds. But the initial comparison suggested that when arsenate bound to the protein, it did so in just the same way as phosphate. Elias suspected that the key might lie in a single, highly unusual bond between a hydrogen atom in the protein and the molecule. This bond had been previously noted but ignored, as phosphate binding occurred with or without it.
To see the difference, the team had to stretch the limits of crystallization technology, getting the resolution to less than one angstrom – fine enough to identify individual hydrogen atoms and compare their bonds. Only then were they able to identify a single disparity: The angles of that unusual hydrogen bond were different. Inside a tight cavity within the PBP structure, phosphate binds at a "textbook angle," according to Elias. The slightly larger arsenate molecule, on the other hand, gets pushed up against the hydrogen and bonds at unnatural, distorted angles. Tawfik thinks that the angle is likely to lead to repulsion between the molecule and other atoms in the cavity, preventing the PBP from passing arsenate into the cell's interior.
Tawfik: "These findings may go beyond the solving of a biological mystery. Because phosphates are scarce in many environments, there is quite a bit of interest in understanding how this crucial resource is taken up by organisms. This first observation of a PBP discrimination mechanism is an exciting demonstration of the exquisite fine tuning that enables proteins to distinguish between two nearly-identical molecules."
### Prof. Dan Tawfik's research is supported by the Adelis Foundation; the estate of Mark Scher; and Ms. Miel de Botton, UK. Prof. Tawfik is the incumbent of the Nella and Leon Benoziyo Professorial Chair.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,700 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
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Rejecting arsentate
2012-10-22
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