Issue 24, 2016

Dynamic ruffling distortion of the heme substrate in non-canonical heme oxygenase enzymes

Abstract

Recent work by several groups has established that MhuD, IsdG, and IsdI are non-canonical heme oxygenases that induce significant out-of-plane ruffling distortions of their heme substrates enroute to mycobilin or staphylobilin formation. However, clear explanations for the observations of “nested” S = ½ VTVH MCD saturation magnetization curves at cryogenic temperatures, and exchange broadened 1H NMR resonances at physiologically-relevant temperatures have remained elusive. Here, MCD and NMR data have been acquired for F23A and F23W MhuD–heme–CN, in addition to MCD data for IsdI–heme–CN, in order to complete assembly of a library of spectroscopic data for cyanide-inhibited ferric heme with a wide range of ruffling deformations. The spectroscopic data were used to evaluate a number of computational models for cyanide-inhibited ferric heme, which ultimately led to the development of an accurate NEVPT2/CASSCF model. The resulting model has a shallow, double-well potential along the porphyrin ruffling coordinate, which provides clear explanations for the unusual MCD and NMR data. The shallow, double-well potential also implies that MhuD-, IsdG-, and IsdI-bound heme is dynamic, and the functional implications of these dynamics are discussed.

Graphical abstract: Dynamic ruffling distortion of the heme substrate in non-canonical heme oxygenase enzymes

Associated articles

Supplementary files

Article information

Article type
Paper
Submitted
22 fev 2016
Accepted
28 may 2016
First published
30 may 2016

Dalton Trans., 2016,45, 10058-10067

Dynamic ruffling distortion of the heme substrate in non-canonical heme oxygenase enzymes

A. B. Graves, E. H. Horak and M. D. Liptak, Dalton Trans., 2016, 45, 10058 DOI: 10.1039/C6DT00702C

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