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Bender GM , Lehmann A , Zou H , Cheng H , Fry HC , Engel D , Therien MJ , Blasie JK , Roder H , Saven JG , DeGrado WF
De novo design of a single-chain diphenylporphyrin metalloprotein
J Am Chem Soc. 2007 Sep 5;129(35) :10732-40
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We describe the computational design of a single-chain four-helix bundle that noncovalently self-assembles with fully synthetic non-natural porphyrin cofactors. With this strategy, both the electronic structure of the cofactor as well as its protein environment may be varied to explore and modulate the functional and photophysical properties of the assembly. Solution characterization (NMR, UV-vis) of the protein showed that it bound with high specificity to the desired cofactors, suggesting that a uniquely structured protein and well-defined site had indeed been created. This provides a genetically expressed single-chain protein scaffold that will allow highly facile, flexible, and asymmetric variations to enable selective incorporation of different cofactors, surface-immobilization, and introduction of spectroscopic probes.
Bender, Gretchen M Lehmann, Andreas Zou, Hongling Cheng, Hong Fry, H Christopher Engel, Don Therien, Michael J Blasie, J Kent Roder, Heinrich Saven, Jeffrey G DeGrado, William F GM071628/GM/United States NIGMS GM54616/GM/United States NIGMS GM61267/GM/United States NIGMS Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States Journal of the American Chemical Society J Am Chem Soc. 2007 Sep 5;129(35):10732-40. Epub 2007 Aug 10.