2ADP

Nitrated Human Manganese Superoxide Dismutase

Summary for 2ADP

• Entry DOI: 10.2210/pdb2adp/pdb
• Descriptor: Superoxide dismutase [Mn], MANGANESE (II) ION, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion matrix: P04179
• Total number of polymer chains: 1
• Total formula weight: 22372.15

Authors

Quint, P.,Reutzel, R.,Mikulski, R.,McKenna, R.,Silverman, D.N. (deposition date: 2005-07-20, release date: 2006-07-04, Last modification date: 2024-04-03)

Primary citation

Quint, P.,Reutzel, R.,Mikulski, R.,McKenna, R.,Silverman, D.N.
Crystal structure of nitrated human manganese superoxide dismutase: mechanism of inactivation.
FREE RADIC.BIOL.MED., 40:453-458, 2006

PubMed Abstract: A cellular consequence of the reaction of superoxide and nitric oxide is enhanced peroxynitrite levels. Reaction of peroxynitrite with manganese superoxide dismutase (MnSOD) causes nitration of the active-site residue Tyr34 and nearly complete inhibition of catalysis. We report the crystal structures at 2.4 A resolution of human MnSOD nitrated by peroxynitrite and the unmodified MnSOD. A comparison of these structures showed no significant conformational changes of active-site residues or solvent displacement. The side chain of 3-nitrotyrosine 34 had a single conformation that extended toward the manganese with O1 of the nitro group within hydrogen-bonding distance (3.1 A) of Nepsilon2 of the second-shell ligand Gln143. Also, nitration of Tyr34 caused a weakening, as evidenced by the lengthening, of a hydrogen bond between its phenolic OH and Gln143, part of an extensive hydrogen-bond network in the active site. Inhibition of catalysis can be attributed to a steric effect of 3-nitrotyrosine 34 that impedes substrate access and binding, and alteration of the hydrogen-bond network that supports proton transfer in catalysis. It is also possible that an electrostatic effect of the nitro group has altered the finely tuned redox potential necessary for efficient catalysis, although the redox potential of nitrated MnSOD has not been measured.

PubMed: 16443160
DOI: 10.1016/j.freeradbiomed.2005.08.045

Experimental method

X-RAY DIFFRACTION (2.4 Å)