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Differential Hydrogen Bonding in Human CYP17 Dictates Hydroxylation versus Lyase Chemistry

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  • This work was supported by the National Institutes of Health grants GM31756 to S.G.S. and R01GM96117 to J.R.K.

Abstract

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Consequences of alternative H-bonding: Raman spectra of oxygenated intermediates of Nanodisc-incorporated human CYP17 in the presence of natural substrates (pregnenolone and progesterone) directly confirm that substrate structure effectively alters hydrogen-bonding interactions with the critical Fe–O–O fragment and dictates its predisposition for one of two alternative reaction pathways. Such substrate control has profound physiological implications.

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