title: Heterodisulfide reductase from Methanothermobacter marburgensis contains an active-site [4Fe-4S] cluster that is directly involved in mediating heterodisulfide reduction.
abstract: Heterodisulfide reductases (HDRs) from methanogenic archaea are iron-sulfur flavoproteins or hemoproteins that catalyze the reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic thiol coenzymes, coenzyme M (CoM-SH) and coenzyme B (CoB-SH). In this work, the ground- and excited-state electronic properties of the paramagnetic Fe-S clusters in Methanothermobacter marburgensis HDR have been characterized using the combination of electron paramagnetic resonance and variable-temperature magnetic circular dichroism spectroscopies. The results confirm multiple S=1/2 [4Fe-4S](+) clusters in dithionite-reduced HDR and reveal spectroscopically distinct S=1/2 [4Fe-4S](3+) clusters in oxidized HDR samples treated separately with the CoM-SH and CoB-SH cosubstrates. The active site of HDR is therefore shown to contain a [4Fe-4S] cluster that is directly involved in mediating heterodisulfide reduction. The catalytic mechanism of HDR is discussed in light of the crystallographic and spectroscopic studies of the related chloroplast ferredoxin:thioredoxin reductase class of disulfide reductases.
authors.affiliation: Max-Planck-Institut für terrestrische Mikrobiologie and Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps-Universität, Karl-von-Frisch-Strasse, D-35043, Marburg, Germany. duin@mailer.uni-marburg.de
authors.forename: Evert C
authors.initials: EC
authors.lastname: Duin
authors.forename: Shahla
authors.initials: S
authors.lastname: Madadi-Kahkesh
authors.forename: Reiner
authors.initials: R
authors.lastname: Hedderich
authors.forename: Michael D
authors.initials: MD
authors.lastname: Clay
authors.forename: Michael K
authors.initials: MK
authors.lastname: Johnson
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D004220:Disulfides / Q000378:metabolism; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D015080:Mesna / Q000378:metabolism; D017013:Methanobacteriaceae / Q000201:enzymology*; D008956:Models, Chemical; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D010769:Phosphothreonine / Q000031:analogs & derivatives* / Q000378:metabolism; D013455:Sulfur / Q000737:chemistry / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D004220:Disulfides; D007506:Iron-Sulfur Proteins; C049349:7-mercaptoheptanoylthreonine phosphate; D010769:Phosphothreonine; D013455:Sulfur; D007501:Iron; D010088:Oxidoreductases; C087171:heterodisulfide reductase; D015080:Mesna