1HL5

The Structure of Holo Type Human Cu, Zn Superoxide Dismutase

Summary for 1HL5

• Entry DOI: 10.2210/pdb1hl5/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1KMG 1L3N 1MFM 1N18 1N19 1SOS 1SPD 4SOD
• Descriptor: SUPEROXIDE DISMUTASE, COPPER (II) ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase, human cu, zn superoxide dismutase, antioxidant, metal-binding, amyotrophic lateral sclerosis, disease mutation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 18
• Total formula weight: 287337.52

Authors

Strange, R.W.,Antonyuk, S.,Hough, M.A.,Doucette, P.,Rodriguez, J.,Hart, P.J.,Hayward, L.J.,Valentine, J.S.,Hasnain, S.S. (deposition date: 2003-03-13, release date: 2003-05-08, Last modification date: 2024-11-13)

Primary citation

Strange, R.W.,Antonyuk, S.,Hough, M.A.,Doucette, P.,Rodriguez, J.,Hart, P.J.,Hayward, L.J.,Valentine, J.S.,Hasnain, S.S.
The Structure of Holo and Metal-Deficient Wild-Type Human Cu, Zn Superoxide Dismutase and its Relevance to Familial Amyotrophic Lateral Sclerosis
J.Mol.Biol., 328:877-, 2003

PubMed Abstract: Cu, Zn superoxide dismutase (SOD1) forms a crucial component of the cellular defence against oxidative stress. Zn-deficient wild-type and mutant human SOD1 have been implicated in the disease familial amyotrophic lateral sclerosis (FALS). We present here the crystal structures of holo and metal-deficient (apo) wild-type protein at 1.8A resolution. The P21 wild-type holo enzyme structure has nine independently refined dimers and these combine to form a "trimer of dimers" packing motif in each asymmetric unit. There is no significant asymmetry between the monomers in these dimers, in contrast to the subunit structures of the FALS G37R mutant of human SOD1 and in bovine Cu,Zn SOD. Metal-deficient apo SOD1 crystallizes with two dimers in the asymmetric unit and shows changes in the metal-binding sites and disorder in the Zn binding and electrostatic loops of one dimer, which is devoid of metals. The second dimer lacks Cu but has approximately 20% occupancy of the Zn site and remains structurally similar to wild-type SOD1. The apo protein forms a continuous, extended arrangement of beta-barrels stacked up along the short crystallographic b-axis, while perpendicular to this axis, the constituent beta-strands form a zig-zag array of filaments, the overall arrangement of which has a similarity to the common structure associated with amyloid-like fibrils.

PubMed: 12729761
DOI: 10.1016/S0022-2836(03)00355-3

Experimental method

X-RAY DIFFRACTION (1.8 Å)