title: Generation of adenosyl radical from S-adenosylmethionine (SAM) in biotin synthase.
abstract: A mechanism of the C-S bond activation of S-adenosylmethionine (SAM) in biotin synthase is discussed from quantum mechanical/molecular mechanical (QM/MM) computations. The active site of the enzyme involves a [4Fe-4S] cluster, which is coordinated to the COO(-) and NH(2) groups of the methionine moiety of SAM. The unpaired electrons on the iron atoms of the [4Fe-4S](2+) cluster are antiferromagnetically coupled, resulting in the S=0 ground spin state. An electron is transferred from an electron donor to the [4Fe-4S](2+)-SAM complex to produce the catalytically active [4Fe-4S](+) state. The SOMO of the [4Fe-4S](+)-SAM complex is localized on the [4Fe-4S] moiety and the spin density of the [4Fe-4S] core is calculated to be 0.83. The C-S bond cleavage is associated with the electron transfer from the [4Fe-4S](+) cluster to the antibonding σ* C-S orbital. The electron donor and acceptor states are effectively coupled with each other at the transition state for the C-S bond cleavage. The activation barrier is calculated to be 16.0 kcal/mol at the QM (B3LYP/SV(P))/MM (CHARMm) level of theory and the C-S bond activation process is 17.4 kcal/mol exothermic, which is in good agreement with the experimental observation that the C-S bond is irreversibly cleaved in biotin synthase. The sulfur atom of the produced methionine molecule is unlikely to bind to an iron atom of the [4Fe-4S](2+) cluster after the C-S bond cleavage from the energetical and structural points of view.
authors.affiliation: Institute for Materials Chemistry and Engineering, Kyushu University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamachi
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kouno
authors.forename: Kazuki
authors.initials: K
authors.lastname: Doitomi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshizawa
mesh_terms: D002384:Catalysis; D004578:Electron Spin Resonance Spectroscopy; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D012436:S-Adenosylmethionine / Q000737:chemistry* / Q000378:metabolism; D013466:Sulfurtransferases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D007506:Iron-Sulfur Proteins; D012436:S-Adenosylmethionine; D013466:Sulfurtransferases; C057985:biotin synthetase