Isaac Yonemoto’s favorite structure is:

Insulin Hexamer (1ai0)

Insulin Hexamer (1ai0)

Source: Selfmade, using PyMol


I’ve loved this structure for over 8 years (I made the similar one, derived from an NMR structure, featured on insulin wikipedia page since ’06). Despite extreme effort to obtain beautiful crystals – some were even grown on the space shuttle – EM diffraction shows no evidence that insulin is crystalline in higher therians. The b-chain strands are in an antiparallel beta sheet, tantalizingly wrong for understanding parallel beta-sheet amyloid assembly of insulin, which occurs via these residues. A hyperconserved lysine (except, oddly, in rodent insulin 1) is very likely salt bridging in ‘real insulin’ but is seen in an artefactual cystallographic interactions in this structure. A calcium ion, believed to reside in biological formulations, is missing, because the inclusion of calcium ions leads to uncontrollable precipitation. In short, these structures, discovered relatively early and continously refined, are symbolic of the human tendency to seek beauty over reality, and for that reason I love it, C3- and pseudo-C2 symmetries and all. But beauty may not necessarily be useless: These structures have been instrumental in guiding the design of the bestiary of reformulated insulins over the decades. —Isaac Yonemoto

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