5eil

Publication Abstract from PubMed

Metal-chelating heteroaryl small molecules have found widespread use as building blocks for coordination-driven, self-assembling nanostructures. The metal-chelating noncanonical amino acid (2,2'-bipyridin-5yl)alanine (Bpy-ala) could, in principle, be used to nucleate specific metalloprotein assemblies if introduced into proteins such that one assembly had much lower free energy than all alternatives. Here we describe the use of the Rosetta computational methodology to design a self-assembling homotrimeric protein with [Fe(Bpy-ala)3]2+ complexes at the interface between monomers. X-ray crystallographic analysis of the homotrimer showed that the design process had near-atomic-level accuracy: The all-atom rmsd between the design model and crystal structure for the residues at the protein interface is approximately 1.4 A. These results demonstrate that computational protein design together with genetically encoded noncanonical amino acids can be used to drive formation of precisely specified metal-mediated protein assemblies that could find use in a wide range of photophysical applications.

Computational design of a homotrimeric metalloprotein with a trisbipyridyl core.,Mills JH, Sheffler W, Ener ME, Almhjell PJ, Oberdorfer G, Pereira JH, Parmeggiani F, Sankaran B, Zwart PH, Baker D Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15012-15017. doi:, 10.1073/pnas.1600188113. Epub 2016 Dec 8. PMID:27940918^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.