2P4K

Contribution to Structure and Catalysis of Tyrosine 34 in Human Manganese Superoxide Dismutase

Summary for 2P4K

• Entry DOI: 10.2210/pdb2p4k/pdb
• Related: 1ZSP 1ZTE 1ZUQ
• Descriptor: Superoxide dismutase, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: mnsod, manganese superoxide dismutase, y34n mutation, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion matrix: P04179
• Total number of polymer chains: 4
• Total formula weight: 88955.92

Authors

Perry, J.J. (deposition date: 2007-03-12, release date: 2007-04-03, Last modification date: 2023-08-30)

Primary citation

Perry, J.J.,Hearn, A.S.,Cabelli, D.E.,Nick, H.S.,Tainer, J.A.,Silverman, D.N.
Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis.
Biochemistry, 48:3417-3424, 2009

PubMed Abstract: Superoxide dismutase (SOD) enzymes are critical in controlling levels of reactive oxygen species (ROS) that are linked to aging, cancer, and neurodegenerative disease. Superoxide (O(2)(*-)) produced during respiration is removed by the product of the SOD2 gene, the homotetrameric manganese superoxide dismutase (MnSOD). Here, we examine the structural and catalytic roles of the highly conserved active-site residue Tyr34, based upon structure-function studies of MnSOD enzymes with mutations at this site. Substitution of Tyr34 with five different amino acids retained the active-site protein structure and assembly but caused a substantial decrease in the catalytic rate constant for the reduction of superoxide. The rate constant for formation of the product inhibition complex also decreases but to a much lesser extent, resulting in a net increase in the level of product inhibited form of the mutant enzymes. Comparisons of crystal structures and catalytic rates also suggest that one mutation, Y34V, interrupts the hydrogen-bonded network, which is associated with a rapid dissociation of the product-inhibited complex. Notably, with three of the Tyr34 mutants, we also observe an intermediate in catalysis, which has not been reported previously. Thus, these mutants establish a means of trapping a catalytic intermediate that promises to help elucidate the mechanism of catalysis.

PubMed: 19265433
DOI: 10.1021/bi8023288

Experimental method

X-RAY DIFFRACTION (1.48 Å)