Beratan, Therien and Collaborators Pack a Porphyrin into a Protein Puzzle

The de novo design of a protein capable of binding a cofactor in a unique orientation is a challenging problem because a range of structurally similar, yet different, complexes are often formed. Now, a team led by former graduate student Nick Polizzi and by Professors David N. Beratan and Michael J. Therien at Duke, and by Professor William F. DeGrado at UCSF, report a protein — designed entirely from first principles — that binds a small-molecule cofactor in a unique and precisely predetermined orientation (shown schematically on the journal cover). Solving this puzzle required the design of a remote protein core that predisposes a flexible binding site to accommodate the porphyrin cofactor in a unique binding geometry.  Read more about this in Nature Chemistry's December issue, available here.