title: The octahaem MccA is a haem c-copper sulfite reductase.
abstract: The six-electron reduction of sulfite to sulfide is the pivot point of the biogeochemical cycle of the element sulfur. The octahaem cytochrome c MccA (also known as SirA) catalyses this reaction for dissimilatory sulfite utilization by various bacteria. It is distinct from known sulfite reductases because it has a substantially higher catalytic activity and a relatively low reactivity towards nitrite. The mechanistic reasons for the increased efficiency of MccA remain to be elucidated. Here we show that anoxically purified MccA exhibited a 2- to 5.5-fold higher specific sulfite reductase activity than the enzyme isolated under oxic conditions. We determined the three-dimensional structure of MccA to 2.2 Å resolution by single-wavelength anomalous dispersion. We find a homotrimer with an unprecedented fold and haem arrangement, as well as a haem bound to a CX15CH motif. The heterobimetallic active-site haem 2 has a Cu(I) ion juxtaposed to a haem c at a Fe-Cu distance of 4.4 Å. While the combination of metals is reminiscent of respiratory haem-copper oxidases, the oxidation-labile Cu(I) centre of MccA did not seem to undergo a redox transition during catalysis. Intact MccA tightly bound SO2 at haem 2, a dehydration product of the substrate sulfite that was partially turned over due to photoreduction by X-ray irradiation, yielding the reaction intermediate SO. Our data show the biometal copper in a new context and function and provide a chemical rationale for the comparatively high catalytic activity of MccA.
authors: Lehrstuhl Biochemie, Institut für Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg, Germany.
authors: Bianca
authors: B
authors: Hermann
authors: Microbial Energy Conversion &Biotechnology, Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.
authors: Melanie
authors: M
authors: Kern
authors: Microbial Energy Conversion &Biotechnology, Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.
authors: Luigi
authors: L
authors: La Pietra
authors: Microbial Energy Conversion &Biotechnology, Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 10, 64287 Darmstadt, Germany.
authors: Jörg
authors: J
authors: Simon
authors: 1] Lehrstuhl Biochemie, Institut für Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg, Germany [2] BIOSS Centre for Biological Signalling Studies, Schänzlestrasse 1, 79104 Freiburg, Germany.
authors: Oliver
authors: O
authors: Einsle
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D003300:Copper / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives* / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D013447:Sulfites / Q000378:metabolism; D013458:Sulfur Dioxide / Q000378:metabolism; D016968:Wolinella / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D013447:Sulfites; C545158:cysteine thiolate; D013458:Sulfur Dioxide; C031690:heme C; D006418:Heme; D003300:Copper; D050862:Oxidoreductases Acting on Sulfur Group Donors; D003545:Cysteine
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