2vr8: Difference between revisions

Revision as of 13:35, 30 April 2008

CRYSTAL STRUCTURE OF G85R ALS MUTANT OF HUMAN CU,ZN SUPEROXIDE DISMUTASE (CUZNSOD) AT 1.36 A RESOLUTION

OverviewOverview

Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). Transgenic mice expressing the human Gly85Arg (G85R) SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfiolding or aggregation of G85R SOD1 induce motor neuron toxicity are 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 CNS 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 ALS.

About this StructureAbout this Structure

2VR8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structures of the G85R variant of SOD1 in Familial ALS., Cao X, Antonyuk S, Seetharaman SV, Whitson LJ, Taylor AB, Holloway SP, Strange RW, Doucette PA, Valentine JS, Tiwari A, Hayward LJ, Padua S, Cohlberg JA, Hasnain SS, Hart PJ, J Biol Chem. 2008 Mar 31;. PMID:18378676 Page seeded by OCA on Wed Apr 30 13:35:42 2008

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OCA

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 '''CRYSTAL STRUCTURE OF G85R ALS MUTANT OF HUMAN CU,ZN SUPEROXIDE DISMUTASE (CUZNSOD) AT 1.36 A RESOLUTION'''
+==Overview==
+Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). Transgenic mice expressing the human Gly85Arg (G85R) SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfiolding or aggregation of G85R SOD1 induce motor neuron toxicity are 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 CNS 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 ALS.
 ==About this Structure==
 VR8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VR8 OCA].
+==Reference==
+Structures of the G85R variant of SOD1 in Familial ALS., Cao X, Antonyuk S, Seetharaman SV, Whitson LJ, Taylor AB, Holloway SP, Strange RW, Doucette PA, Valentine JS, Tiwari A, Hayward LJ, Padua S, Cohlberg JA, Hasnain SS, Hart PJ, J Biol Chem. 2008 Mar 31;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18378676 18378676]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
@@ Line 44: / Line 50: @@
 [[Category: Zinc]]
 [[Category: Zn superoxide dismutase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:35:42 2008''