4B3E

Structure of copper-zinc superoxide dismutase complexed with bicarbonate.

Summary for 4B3E

• Entry DOI: 10.2210/pdb4b3e/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1HL5 1KMG 1L3N 1MFM 1N18 1N19 1OEZ 1OZT 1OZU 1P1V 1PTZ 1PU0 1RK7 1SOS 1SPD 1UXL 1UXM 2AF2 2C9S 2C9U 2C9V 2V0A 2VR6 2VR7 2VR8 2WKO 2WYT 2WYZ 2WZ0 2WZ5 2WZ6 2XJK 2XJL 4A7G 4A7Q 4A7R 4A7S 4A7T 4A7U 4A7V 4SOD
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], COPPER (II) ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 10
• Total formula weight: 161957.52

Authors

Strange, R.W.,Hough, M.A.,Antonyuk, S.V.,Hasnain, S.S. (deposition date: 2012-07-23, release date: 2012-09-26, Last modification date: 2024-10-23)

Primary citation

Strange, R.W.,Hough, M.A.,Antonyuk, S.V.,Hasnain, S.S.
Structural Evidence for a Copper-Bound Carbonate Intermediate in the Peroxidase and Dismutase Activities of Superoxide Dismutase.
Plos One, 7:44811-, 2012

PubMed Abstract: Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our understanding of oxidative damage. Its primary function is catalysing the dismutation of superoxide to O(2) and H(2)O(2). SOD also reacts with H(2)O(2), leading to the formation of a strong copper-bound oxidant species that can either inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate (or CO(2)) and H(2)O(2), this peroxidase activity is enhanced and produces the carbonate radical. This freely diffusible reactive oxygen species is proposed as the agent for oxidation of large substrates that are too bulky to enter the active site. Here, we provide direct structural evidence, from a 2.15 Å resolution crystal structure, of (bi)carbonate captured at the active site of reduced SOD, consistent with the view that a bound carbonate intermediate could be formed, producing a diffusible carbonate radical upon reoxidation of copper. The bound carbonate blocks direct access of substrates to Cu(I), suggesting that an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled electron transfer mechanism involving the bound carbonate rather than the solvent. Carbonate is captured in a different site when SOD is oxidised, being located in the active site channel adjacent to the catalytically important Arg143. This is the probable route of diffusion from the active site following reoxidation of the copper. In this position, the carbonate is poised for re-entry into the active site and binding to the reduced copper.

PubMed: 22984565
DOI: 10.1371/JOURNAL.PONE.0044811

Experimental method

X-RAY DIFFRACTION (2.15 Å)