Our immediate goal in the human and anEc-TFE and C-P4H projects is to crystallize these enzymes and determine their crystal structures. The structural information will then be used to understand their function. For MtTFE, we will carry out crystallographic binding studies and computational studies (in collaboration with Mroginsky, TU-Berlin) to elucidate its substrate specificity. For MFE1 and TFE it has been observed that the product of the first active site is ‘channelled’ to the second active site without being relased in bulk solvent. Our research on MFE1 will focus on understanding the mechanism of this substrate channelling. In addition, in the long term, our structural enzymology studies provide insight that can facilitate the use of natural enzymes for the synthesis of desirable chemicals using more sustainable production methods. Also, we will put considerable efforts into understanding the reaction mechanisms of these enzymes by extending our studies towards discovering high affinity transition state analogues (with Schramm, Albert Einstein College, New York). These compounds capture key structural features of the transition state of the enzyme catalysed reaction (Schramm, 2015) and consequently can have picomolar affinity and are important for understanding the respective reaction mechanisms. Such compounds can also be exploited in drug discovery research projects.
Viimeksi päivitetty: 28.10.2016