High resolution structure of a high energy protein state

• Applicant: Professor Dr. Michael Kovermann
• Subject Area: Structural Biology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 235527726

Macromolecular recognition is important for numerous cellular processes, spanning from enzymatic reactions to protein- protein interactions during for instance transcription. From energetic and static structural perspectives, detailed understanding of interactions between macromolecules has been obtained by researchers at the interface of structural biology and biophysics. This proposal focuses on specific aspects of macromolecular recognition that remain unresolved. Within the proposed project I want to answer a crucial question in the field of molecular recognition namely: do proteins make structural excursions all the way to bound-like structures in the absence of any substrate? This is a fundamental question that is relevant for many (if not all) proteins that interacts with small molecules or protein substrates. Moreover, this project has the potential to deliver a high resolution structure of an exited protein state determined from direct structural restraints. The methodology developed here can, in principle, be applied to many other systems were proteins are believed to transiently populate high energy structural states. Specific aims of this proposal: 1) Trap E. coli adenylate kinase in excited (naturally low populated) states using disulfide chemistry 2) Determine the high resolution structure of an excited state with solution state NMR methodology.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professor Dr. Magnus Wolf-Watz