1UXL

I113T mutant of human SOD1

Summary for 1UXL

• Entry DOI: 10.2210/pdb1uxl/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1HL5 1KMG 1L3N 1MFM 1N18 1N19 1OEZ 1OZT 1OZU 1P1V 1PTZ 1PU0 1RK7 1SOS 1SPD 1UXM 4SOD
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], COPPER (II) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: human cu, zn superoxide dismutase, antioxidant, metal- binding, amyotrophic lateral sclerosis, disease mutation, oxidoreductase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 10
• Total formula weight: 160213.13

Authors

Hough, M.A.,Grossmann, J.G.,Antonyuk, S.V.,Strange, R.W.,Doucette, P.A.,Rodriguez, J.A.,Whitson, L.J.,Hart, P.J.,Hayward, L.J.,Valentine, J.S.,Hasnain, S.S. (deposition date: 2004-02-25, release date: 2004-03-19, Last modification date: 2024-11-13)

Primary citation

Hough, M.A.,Grossmann, J.G.,Antonyuk, S.V.,Strange, R.W.,Doucette, P.A.,Rodriguez, J.A.,Whitson, L.J.,Hart, P.J.,Hayward, L.J.,Valentine, J.S.,Hasnain, S.S.
Dimer Destabilization in Superoxide Dismutase May Result in Disease-Causing Properties: Structures of Motor Neuron Disease Mutants
Proc.Natl.Acad.Sci.USA, 101:5976-, 2004

PubMed Abstract: More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body of evidence suggests that a subset of mutations located close to the dimeric interface can lead to a major destabilization of the mutant enzymes. We have determined the crystal structures of the Ala4Val (A4V) and Ile113Thr (I113T) mutants to 1.9 and 1.6 A, respectively. In the A4V structure, small changes at the dimer interface result in a substantial reorientation of the two monomers. This effect is also seen in the case of the I113T crystal structure, but to a smaller extent. X-ray solution scattering data show that in the solution state, both of the mutants undergo a more pronounced conformational change compared with wild-type superoxide dismutase (SOD) than that observed in the A4V crystal structure. Shape reconstructions from the x-ray scattering data illustrate the nature of this destabilization. Comparison of these scattering data with those for bovine CuZn SOD measured at different temperatures shows that an analogous change in the scattering profile occurs for the bovine enzyme in the temperature range of 70-80 degrees C. These results demonstrate that the A4V and I113T mutants are substantially destabilized in comparison with wild-type SOD1, and it is possible that the pathogenic properties of this subset of familial amyotrophic lateral sclerosis mutants are at least in part due to this destabilization.

PubMed: 15056757
DOI: 10.1073/PNAS.0305143101

Experimental method

X-RAY DIFFRACTION (1.6 Å)