Probing water micro-solvation in proteins by water catalysed proton-transfer tautomerism

Scientists have made tremendous efforts to gain understanding of the water molecules in proteins via indirect measurements such as molecular dynamic simulation and/or probing the polarity of the local environment. Here we present a tryptophan analogue that exhibits remarkable water catalysed proton-transfer properties. The resulting multiple emissions provide unique fingerprints that can be exploited for direct sensing of a site-specific water environment in a protein without disrupting its native structure. Replacing tryptophan with the newly developed tryptophan analogue we sense different water environments surrounding the five tryptophans in human thromboxane A 2 synthase. This development may lead to future research to probe how water molecules affect the folding, structures and activities of proteins. Detailed knowledge of the water environment within proteins may lead to an increased understanding of protein folding and function. Here the authors present a tryptophan analogue with remarkable water catalysed proton-transfer properties that may be exploited for site-specific water sensing.