normal hydrogen electrode at pH 9.0), which is strongly coupled to proton binding, as designed.ĭe novo designed proteins show promise as robust, simplified working models, maquettes, with which to determine structure–function relationships that are obscured in their much more complicated natural counterparts ( 1– 5). Oxidation-reduction of both hemes displays an unusually low midpoint potential (–248 mV vs. The transition to structured holomaquette involved the alteration of 6 of 31 residues in each of the four identical helices and, unlike our earlier efforts, required no design intermediates. Heme insertion was modeled with angular constraints statistically derived from natural proteins, and the pattern of hydrophobic and hydrophilic residues on each helix was then altered to account for this large structural reorganization. 元1M was functionally redesigned to accommodate two hemes ligated to histidines and to retain the strong coupling of heme oxidation-reduction to glutamate acid–base transitions and proton exchange that was characterized in molten globule predecessors. The HP-1 design strategy began with the x-ray crystal structure of the apomaquette 元1M, an apomaquette derived from the structurally heterogeneous tetraheme-binding H10H24 prototype. We report here the design and synthesis of HP-1, a disulfide-bridged two-α-helix peptide that self-assembles to form an antiparallel twofold symmetric diheme four-α-helix bundle protein with a stable conformation on the NMR time-scale.
MAQUETTE UPDATE FULL
Despite successful inclusion of several key functional elements of natural proteins into a family of heme protein maquettes, the lack of 3D structures, due principally to conformational heterogeneity, has prevented them from achieving their full potential. So too, an interest in Magic: The Gathering has persisted since William’s youth, and he can frequently be found watching Magic streams on Twitch and reading over the latest set spoilers.Synthetic heme-binding four-α-helix bundles show promise as working model systems, maquettes, for understanding heme cofactor–protein assembly and function in oxidoreductases.
MAQUETTE UPDATE SOFTWARE
Now, William enjoys playing Super Mario Maker 2 on the Switch with his daughter and finding time to sneak in the newest From Software game when possible.
This interest reached a height with MMORPGs like Asheron’s Call 2, Star Wars Galaxies, and World of Warcraft, on which William spent considerable time up until college. William’s first console was the NES, but when he was eight, it was The Legend of Zelda: Link’s Awakening on Game Boy that fully cemented his interest in the format. All the while, William’s passion for games remained. Upon graduating from the University of Southern California’s School of Cinematic Arts, William entered the realm of fine arts administration, assisting curators, artists, and fine art professionals with the realization of contemporary art exhibitions. William Parks is an editor at Game Rant with a background in visual arts.