First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity
GGA+U methodology details and explanation, linear-response U values, U dependent splittings, bond lengths, reaction steps, dissociation energies, occupation matrices and oxidation states, and additional structural parameters. This material is available free of charge via the Internet at http://pubs....
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society
2011
|
| Online Access: | http://hdl.handle.net/1721.1/67699 https://orcid.org/0000-0001-5486-2755 https://orcid.org/0000-0001-9342-0191 |
| _version_ | 1811093837044514816 |
|---|---|
| author | Kulik, Heather Janine Blasiak, Leah C. Marzari, Nicola Drennan, Catherine L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kulik, Heather Janine Blasiak, Leah C. Marzari, Nicola Drennan, Catherine L. |
| author_sort | Kulik, Heather Janine |
| collection | MIT |
| description | GGA+U methodology details and explanation, linear-response U values, U dependent splittings, bond lengths, reaction steps, dissociation energies, occupation matrices and oxidation states, and additional structural parameters. This material is available free of charge via the Internet at http://pubs.acs.org. |
| first_indexed | 2024-09-23T15:51:29Z |
| format | Article |
| id | mit-1721.1/67699 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:51:29Z |
| publishDate | 2011 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/676992022-09-29T16:35:54Z First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity Kulik, Heather Janine Blasiak, Leah C. Marzari, Nicola Drennan, Catherine L. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Materials Science and Engineering Drennan, Catherine L Kulik, Heather Janine Blasiak, Leah C. Marzari, Nicola Drennan, Catherine L. GGA+U methodology details and explanation, linear-response U values, U dependent splittings, bond lengths, reaction steps, dissociation energies, occupation matrices and oxidation states, and additional structural parameters. This material is available free of charge via the Internet at http://pubs.acs.org. We present here a computational study of reactions at a model complex of the SyrB2 enzyme active site. SyrB2, which chlorinates l-threonine in the syringomycin biosynthetic pathway, belongs to a recently discovered class of α-ketoglutarate (αKG), non-heme Fe(II)-dependent halogenases that share many structural and chemical similarities with hydroxylases. Namely, halogenases and hydroxylases alike decarboxylate the αKG co-substrate, facilitating formation of a high-energy ferryl-oxo intermediate that abstracts a hydrogen from the reactant complex. The reaction mechanisms differ at this point, and mutation of active site residues (Asp for the hydroxylase to Ala or Ala to Asp/Glu for halogenase) fails to reproduce hydroxylating activity in SyrB2 or halogenating activity in similar hydroxylases. Using a density functional theory approach with a recently implemented Hubbard U correction for accurate treatment of transition-metal chemistry, we explore probable reaction pathways and mechanisms via a model complex consisting of only the iron center and its direct ligands. We show that the first step, αKG decarboxylation, is barrierless and exothermic, but the subsequent hydrogen abstraction step has an energetic barrier consistent with that accessible under biological conditions. In the model complex we use, radical chlorination is barrierless and exothermic, whereas the analogous hydroxylation is found to have a small energetic barrier. The hydrogen abstraction and radical chlorination steps are strongly coupled: the barrier for the hydrogen abstraction step is reduced when carried out concomitantly with the exothermic chlorination step. Our work suggests that the lack of chlorination in mutant hydroxylases is most likely due to poor binding of chlorine in the active site, whereas mutant halogenases do not hydroxylate for energetic reasons. Although secondary shell residues undoubtedly modulate the overall reactivity and binding of relevant substrates, we show that a small model compound consisting exclusively of the direct ligands to the metal can help explain reactivity heretofore not yet understood in the halogenase SyrB2. National Institutes of Health (U.S.) (GM65337) National Institutes of Health (U.S.) (T32-GM08334) United States. Dept. of Energy (DE-AC04-94AL850000) 2011-12-15T19:09:46Z 2011-12-15T19:09:46Z 2009-09 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/67699 Kulik, Heather J. et al. “First-Principles Study of Non-heme Fe(II) Halogenase SyrB2 Reactivity.” Journal of the American Chemical Society 131 (2009): 14426-14433. Web. 15 Dec. 2011. © 2011 American Chemical Society https://orcid.org/0000-0001-5486-2755 https://orcid.org/0000-0001-9342-0191 en_US http://dx.doi.org/10.1021/ja905206k Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society Prof. Drennan via Erja Kajosalo |
| spellingShingle | Kulik, Heather Janine Blasiak, Leah C. Marzari, Nicola Drennan, Catherine L. First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity |
| title | First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity |
| title_full | First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity |
| title_fullStr | First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity |
| title_full_unstemmed | First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity |
| title_short | First-principles study of non-heme Fe(II) halogenase SyrB2 reactivity |
| title_sort | first principles study of non heme fe ii halogenase syrb2 reactivity |
| url | http://hdl.handle.net/1721.1/67699 https://orcid.org/0000-0001-5486-2755 https://orcid.org/0000-0001-9342-0191 |
| work_keys_str_mv | AT kulikheatherjanine firstprinciplesstudyofnonhemefeiihalogenasesyrb2reactivity AT blasiakleahc firstprinciplesstudyofnonhemefeiihalogenasesyrb2reactivity AT marzarinicola firstprinciplesstudyofnonhemefeiihalogenasesyrb2reactivity AT drennancatherinel firstprinciplesstudyofnonhemefeiihalogenasesyrb2reactivity |