Any feedback?
Literature summary for 1.8.99.5 extracted from
- The octahaem MccA is a haem c-copper sulfite reductase (2015), Nature, 520, 706-709 .
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| purified enzyme, X-ray diffraction structure determination and analysis at 2.2 A resolution, single-wavelength anomalous dispersion | Wolinella succinogenes |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Cu | the heterobimetallic active-site heme 2 has a Cu(I) ion juxtaposed to a heme c at a Fe-Cu distance of 4.4 A. While the combination of metals is reminiscent of respiratory hemecopper oxidases, the oxidation-labile Cu(I) centre of MccA does not seem to undergo a redox transition during catalysis. The copper-depleted form II of MccA, the absence of the heterometal allows for a binding mode of sulfite that is similar to the one seen in the siroheme-containing enzymes or in NrfA. In the structure of the Cu-containing, high-activity form I of MccA, all 12 monomers in the asymmetric unit have a ligand bound to heme 2 | Wolinella succinogenes |  |
| Fe | the heterobimetallic active-site heme 2 has a Cu(I) ion juxtaposed to a heme c at a Fe-Cu distance of 4.4 A | Wolinella succinogenes | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Wolinella succinogenes | multiheme cytochrome c enzymes catalyse complex-multi-electron redox reactions and bind their substrates through the free electron pairs of a heteroatom to a free coordination position at an active-site hem group. Electrons are then provided or accepted by the tightly coupled chain of heme groups | ? | - |
? | |
| sulfite + 6 ferrocytochrome c + 6 H+ | Wolinella succinogenes | overall transfer of 6 electrons during the reaction | sulfide + 6 ferricytochrome c + 3 H2O | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Wolinella succinogenes | Q7MSJ8 | - |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| hydrogen sulfide + a [DsrC protein]-disulfide + 2 acceptor + 3 H2O = sulfite + a [DsrC protein]-dithiol + 2 reduced acceptor + 2 H+ | sulfite is bound at an oxidation state of S1IV and immediately dehydrated. All oxygen atoms are fixed in a tight hydrogen-bonding network, upon transfer of two electrons to yield an S1II state, a second oxygen atom is released as water, but held within the active-site cavity. A further two-electron reduction leads to the S0 state, weakening the remaining S-O bond. With the final transfer of two electrons, the state of sulfide (S2II) is reached and a third water is released, catalytic mechanism overview. The heterobimetallic active-site heme 2 has a Cu(I) ion juxtaposed to a heme c at a Fe-Cu distance of 4.4 A. While the combination of metals is reminiscent of respiratory heme-copper oxidases, the oxidation-labile Cu(I) centre of MccA does not seem to undergo a redox transition during catalysis. Intact MccA tightly binds SO2 at heme 2, a dehydration product of the substrate sulfite that is partially turned over due to photoreduction by X-ray irradiation, yielding the reaction intermediate SO. Structure of sulfite reduction at heme2 of MccA, sulfite binds to the resting state of the enzyme, but the active-site architecture shifts the reversible dehydration equilibrium to SO2 + H2O. Reduction by two electrons occurs through photoreduction in the X-ray beam and leads to release of a second H2O after protonation, with SO remaining bound to the active site. A tight network of hydrogen bonds surrounds the bimetal centre and the bound substrate, holding the reaction products in place. The sulfite substrate only oxidizes half the heme groups of reduced MccA, emphasizing that the total electron charge of the multiheme enzyme is of high relevance for catalysis | Wolinella succinogenes |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | multiheme cytochrome c enzymes catalyse complex-multi-electron redox reactions and bind their substrates through the free electron pairs of a heteroatom to a free coordination position at an active-site hem group. Electrons are then provided or accepted by the tightly coupled chain of heme groups | Wolinella succinogenes | ? | - |
? | |
| additional information | MccA reduces sulfite, but not arsenate, selenate, selenite, hydroxylamine, hydrazine, fumarate, nitrate, thiosulfate, tetrathionate, polysulfide, or Fe(III). Nitrite is reduced only very slowly to ammonium | Wolinella succinogenes | ? | - |
? | |
| sulfite + 6 ferrocytochrome c + 6 H+ | overall transfer of 6 electrons during the reaction | Wolinella succinogenes | sulfide + 6 ferricytochrome c + 3 H2O | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homotrimer | with an unprecedented fold and heme arrangement, three-dimensional structure analysis | Wolinella succinogenes |
| More | in the CX15CH motif of heme 8, the extended region between the two cysteine residues forms a loop with a short helical turn, in direct vicinity to another loop harbouring the only non-proline cis peptide in the enzyme, between residues G508 and F509. Its formation might require the essential peptidyl isomerase MccB2, and it is presumed to be a prerequisite for correct folding of the loop in the maturation process of heme 8, which is likely to be attached by the dedicated cytochrome c synthase CcsA1. The structure of the CX15CH heme c binding motif disrupts the general parallel/perpendicular heme stacking sequence, and rotates the heme out of plane, possibly to optimize the interaction with the putative electron donor, the iron-sulfur protein MccC | Wolinella succinogenes |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| octahaemcytochrome c MccA | - |
Wolinella succinogenes |
| SiRA | - |
Wolinella succinogenes |
| sulfite reductase | - |
Wolinella succinogenes |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| cytochrome c | octaheme cytochrome | Wolinella succinogenes | |
| heme | octaheme cytochrome, a homotrimer with an unprecedented fold and heme arrangement, as well as a heme bound to a CX15CH motif. The heterobimetallic active-site heme 2 has a Cu(I) ion juxtaposed to a heme c at a Fe-Cu distance of 4.4 A, active-site heme 2 is bound to a canonical CXXCH motif with H306 as a proximal axial ligand. In the CX15CH motif of heme 8, the extended region between the two cysteine residues forms a loop with a short helical turn, in direct vicinity to another loop harbouring the only non-proline cis peptide in the enzyme, between residues G508 and F509. Its formation might require the essential peptidyl isomerase MccB2, and it is presumed to be a prerequisite for correct folding of the loop in the maturation process of heme 8, which is likely to be attached by the dedicated cytochrome c synthase CcsA1. The structure of the CX15CH heme c binding motif disrupts the general parallel/perpendicular heme stacking sequence, and rotates the heme out of plane, possibly to optimize the interaction with the putative electron donor, the iron-sulfur protein MccC | Wolinella succinogenes | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | MccA belongs to the genetically diverse family of multiheme c enzymes and has eight heme groups covalently attached to conserved heme-binding motifs in the peptide sequence. Multiheme cytochrome c enzymes show a high conservation of heme group arrangements, but not of sequence, with recurring heme-packing motifs that result in either a parallel or a perpendicular packing of two of the moieties. They catalyse complexmulti-electron redox reactions and bind their substrates through the free electron pairs of a heteroatom to a free coordination position at an active-site hem group. Electrons are then provided or accepted by the tightly coupled chain of heme groups | Wolinella succinogenes |
| additional information | anoxically purified MccA exhibits a 2 to 5.5fold higher specific sulfite reductase activity than the enzyme isolated under oxic conditions. Presence of two cysteine residues, C399 and C495, juxtaposed at the distal side of the active-site cavity. The active site is a shallow cavity on the distal side of heme 2, lined by residues K208, Y285, Y301, R366 and K393, which are conserved among MccA orthologues | Wolinella succinogenes |
| physiological function | the Epsilonproteobacterium Wolinella succinogenes does not encode a siroheme sulfite reductase and the nrfA gene is not induced during sulfite respiration. Instead, sulfite is reduced by the octaheme c-type cytochrome MccA, with sulfide as the sole product. The enzyme MccA catalyzes the six-electron reduction of sulfite to sulfide, the pivot point of the biogeochemical cycle of the element sulfur for dissimilatory sulfite utilization. It is distinct from known sulfite reductases because it has a substantially higher catalytic activity and a relatively low reactivity towards nitrite | Wolinella succinogenes |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
