Sequential oxidations of thiolates and the cobalt metallocenter in a synthetic metallopeptide

Implications for the biosynthesis of nitrile hydratase

Arnab Dutta, Marco Flores, Souvik Roy, Jennifer C. Schmitt, G. Alexander Hamilton, Hilairy Hartnett, Jason M. Shearer, Anne Jones

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cobalt nitrile hydratases (Co-NHase) contain a catalytic cobalt(III) ion coordinated in an N2S3 first coordination sphere composed of two amidate nitrogens and three cysteine-derived sulfur donors: a thiolate (-SR), a sulfenate (-S(R)O-), and a sulfinate (-S(R)O 2 -). The sequence of biosynthetic reactions that leads to the post-translational oxidations of the metal and the sulfur ligands is unknown, but the process is believed to be initiated directly by oxygen. Herein we utilize cobalt bound in an N2S2 first coordination sphere by a seven amino acid peptide known as SODA (ACDLPCG) to model this oxidation process. Upon exposure to oxygen, Co-SODA is oxidized in two steps. In the first fast step (seconds), magnetic susceptibility measurements demonstrated that the metallocenter remains paramagnetic, that is, Co 2+, and sulfur K-edge X-ray absorption spectroscopy (XAS) is used to show that one of the thiolates is oxidized to sulfinate. In a second process on a longer time scale (hours), magnetic susceptibility measurements and Co K-edge XAS show that the metal is oxidized to Co3+. Unlike other model complexes, additional slow oxidation of the second thiolate in Co-SODA is not observed, and a catalytically active complex is never formed. The likely reason is the absence of the axial thiolate ligand. In essence, the reactivity of Co-SODA can be described as between previously described models which either quickly convert to final product or are stable in air, and it offers a first glimpse into a possible oxidation pathway for nitrile hydratase biosynthesis.

Original languageEnglish (US)
Pages (from-to)5236-5245
Number of pages10
JournalInorganic Chemistry
Volume52
Issue number9
DOIs
StatePublished - May 6 2013

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biosynthesis
Biosynthesis
nitriles
Cobalt
cobalt
Sulfur
Oxidation
oxidation
X ray absorption spectroscopy
sulfur
Magnetic susceptibility
absorption spectroscopy
Metals
Oxygen
Ligands
magnetic permeability
ligands
cysteine
oxygen
metals

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry

Cite this

Sequential oxidations of thiolates and the cobalt metallocenter in a synthetic metallopeptide : Implications for the biosynthesis of nitrile hydratase. / Dutta, Arnab; Flores, Marco; Roy, Souvik; Schmitt, Jennifer C.; Hamilton, G. Alexander; Hartnett, Hilairy; Shearer, Jason M.; Jones, Anne.

In: Inorganic Chemistry, Vol. 52, No. 9, 06.05.2013, p. 5236-5245.

Research output: Contribution to journalArticle

Dutta, Arnab ; Flores, Marco ; Roy, Souvik ; Schmitt, Jennifer C. ; Hamilton, G. Alexander ; Hartnett, Hilairy ; Shearer, Jason M. ; Jones, Anne. / Sequential oxidations of thiolates and the cobalt metallocenter in a synthetic metallopeptide : Implications for the biosynthesis of nitrile hydratase. In: Inorganic Chemistry. 2013 ; Vol. 52, No. 9. pp. 5236-5245.
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