2VR8

Crystal Structure of G85R ALS mutant of Human Cu,Zn Superoxide Dismutase (CuZnSOD) at 1.36 A resolution

Summary for 2VR8

• Entry DOI: 10.2210/pdb2vr8/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 4SOD
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], COPPER (II) ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: zinc, copper, human cu, cytoplasm, acetylation, ubl conjugation, disease mutation, zn superoxide dismutase, amyotrophic lateral sclerosis, antioxidant, metal-binding, oxidoreductase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 2
• Total formula weight: 32883.48

Authors

Antonyuk, S.,Cao, X.,Seetharaman, S.V.,Whitson, L.J.,Taylor, A.B.,Holloway, S.P.,Strange, R.W.,Doucette, P.A.,Tiwari, A.,Hayward, L.J.,Padua, S.,Cohlberg, J.A.,Selverstone Valentine, J.,Hasnain, S.S.,Hart, P.J. (deposition date: 2008-03-28, release date: 2008-04-08, Last modification date: 2024-11-20)

Primary citation

Cao, X.,Antonyuk, S.,Seetharaman, S.V.,Whitson, L.J.,Taylor, A.B.,Holloway, S.P.,Strange, R.W.,Doucette, P.A.,Tiwari, A.,Hayward, L.J.,Padua, S.,Cohlberg, J.A.,Selverstone Valentine, J.,Hasnain, S.S.,Hart, P.J.
Structures of the G85R Variant of Sod1 in Familial Amyotrophic Lateral Sclerosis.
J.Biol.Chem., 283:16169-, 2008

PubMed Abstract: Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis.

PubMed: 18378676
DOI: 10.1074/JBC.M801522200

Experimental method

X-RAY DIFFRACTION (1.36 Å)