Compound I in heme thiolate enzymes : A comparative QM/MM study

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Kyung-Bin Cho
  • Hui Chen
  • Maria Angels Carvajal
  • Shimrit Cohen
  • Etienne Derat
  • Walter Thiel
  • Sason Shaik

Detail(s)

Original languageEnglish
Pages (from-to)13128-13138
Journal / PublicationJournal of Physical Chemistry A
Volume112
Issue number50
Publication statusPublished - 18 Dec 2008
Externally publishedYes

Abstract

This study directly compares the active species of heme enzymes, so-called Compound I (Cpd I), across the heme-thiolate enzyme family. Thus, sixty-four different Cpd I structures are calculated by hybrid quantum mechanical/molecular mechanical (QM/MM) methods using four different cysteine-ligated heme enzymes (P450cam, the mutant P450cam-L358P, CPO and NOS) with varying QM region sizes in two multiplicities each. The overall result is that these Cpd I species are similar to each other with regard to many characteristic features. Hence, using the more stable CPO Cpd I as a model for P450 Cpd I in experiments should be a reasonable approach. However, systematic differences were also observed, and it is shown that NOS stands out in most comparisons. By analyzing the electrical field generated by the enzyme on the QM region, one can see that (a) the protein exerts a large influence and modifies all the Cpd I species compared with the gas-phase situation and (b) in NOS this field is approximately planar to the heme plane, whereas it is approximately perpendicular in the other enzymes, explaining the deviating results on NOS. The calculations on the P450cam mutant L358P show that the effects of removing the hydrogen bond between the heme sulfur and L358 are small at the Cpd I stage. Finally, Mössbauer parameters are calculated for the different Cpd I species, enabling future comparisons with experiments. These results are discussed in the broader context of recent findings of Cpd I species that exhibit large variations in the electronic structure due to the presence of the substrate. © 2008 American Chemical Society.

Citation Format(s)

Compound I in heme thiolate enzymes : A comparative QM/MM study. / Cho, Kyung-Bin; Hirao, Hajime; Chen, Hui et al.

In: Journal of Physical Chemistry A, Vol. 112, No. 50, 18.12.2008, p. 13128-13138.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review