De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex.

Abstract

The de novo design of membrane proteins remains difficult despite recent advances in understanding the factors that drive membrane protein folding and association. We have designed a membrane protein PRIME (PoRphyrins In MEmbrane) that positions two non-natural iron diphenylporphyrins (Fe(III)DPP's) sufficiently close to provide a multicentered pathway for transmembrane electron transfer. Computational methods previously used for the design of multiporphyrin water-soluble helical proteins were extended to this membrane target. Four helices were arranged in a D(2)-symmetrical bundle to bind two Fe(II/III) diphenylporphyrins in a bis-His geometry further stabilized by second-shell hydrogen bonds. UV-vis absorbance, CD spectroscopy, analytical ultracentrifugation, redox potentiometry, and EPR demonstrate that PRIME binds the cofactor with high affinity and specificity in the expected geometry.

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Citation

Published Version (Please cite this version)

10.1021/ja107487b

Publication Info

Korendovych, Ivan V, Alessandro Senes, Yong Ho Kim, James D Lear, H Christopher Fry, Michael J Therien, J Kent Blasie, F Ann Walker, et al. (2010). De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex. J Am Chem Soc, 132(44). pp. 15516–15518. 10.1021/ja107487b Retrieved from https://hdl.handle.net/10161/4046.

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Scholars@Duke

Therien

Michael J. Therien

William R. Kenan, Jr. Distinguished Professor of Chemistry

Our research involves the synthesis of compounds, supermolecular assemblies, nano-scale objects, and electronic materials with unusual ground-and excited-state characteristics, and interrogating these structures using state-of-the-art transient optical, spectroscopic, photophysical, and electrochemical methods. Research activities span physical inorganic chemistry, physical organic chemistry, synthetic chemistry, bioinorganic chemistry, spectroscopy, photophysics, excited-state dynamics, spintronics, and imaging. My laboratory: (i) designs chromophores and supermolecules that display exceptional opto-electronic properties and elucidates their excited-state dynamics, (ii) engineers highly conjugated molecular structures for optical limiting, specialized emission, and high charge mobility, (iii) designs conjugated materials and hybrid molecular-nanoscale structures for energy conversion reactions, (iv) develops molecular wires that propagate spin-polarized currents, (v) fabricates emissive nanoscale structures for in vivo optical imaging, (vi) engineers de novo transition metal cofactor-binding proteins that test light-driven biological energy transducing mechanisms and realize opto-electronic functionalities not found in nature, and (vii) designs and interrogates complex molecular and nanoscale assemblies in which ultrafast energy and charge migration reactions are controlled by quantum coherence effects.


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