{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Antonyuk S"],"funding":["NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["1201-13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2253262"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(5)"],"pubmed_abstract":["The His46Arg (H46R) mutant of human copper-zinc superoxide dismutase (SOD1) is associated with an unusual, slowly progressing form of familial amyotrophic lateral sclerosis (FALS). Here we describe in detail the crystal structures of pathogenic H46R SOD1 in the Zn-loaded (Zn-H46R) and metal-free (apo-H46R) forms. The Zn-H46R structure demonstrates a novel zinc coordination that involves only three of the usual four liganding residues, His 63, His 80, and Asp 83 together with a water molecule. In addition, the Asp 124 \"secondary bridge\" between the copper- and zinc-binding sites is disrupted, and the \"electrostatic loop\" and \"zinc loop\" elements are largely disordered. The apo-H46R structure exhibits partial disorder in the electrostatic and zinc loop elements in three of the four dimers in"],"journal":["Protein science : a publication of the Protein Society"],"pubmed_title":["Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg."],"pmcid":["PMC2253262"],"funding_grant_id":["R01 GM028222","NS39112","NS44170","R01 NS039112","GM28222","R01 NS044170"],"pubmed_authors":["Antonyuk S","Doucette PA","Rodriguez JA","Elam JS","Hasnain SS","Hayward LJ","Strange RW","Valentine JS","Hart PJ","Hough MA"],"additional_accession":[]},"is_claimable":false,"name":"Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg.","description":"The His46Arg (H46R) mutant of human copper-zinc superoxide dismutase (SOD1) is associated with an unusual, slowly progressing form of familial amyotrophic lateral sclerosis (FALS). Here we describe in detail the crystal structures of pathogenic H46R SOD1 in the Zn-loaded (Zn-H46R) and metal-free (apo-H46R) forms. The Zn-H46R structure demonstrates a novel zinc coordination that involves only three of the usual four liganding residues, His 63, His 80, and Asp 83 together with a water molecule. In addition, the Asp 124 \"secondary bridge\" between the copper- and zinc-binding sites is disrupted, and the \"electrostatic loop\" and \"zinc loop\" elements are largely disordered. The apo-H46R structure exhibits partial disorder in the electrostatic and zinc loop elements in three of the four dimers in","dates":{"release":"2005-01-01T00:00:00Z","publication":"2005 May","modification":"2025-05-29T20:33:22.429Z","creation":"2019-03-27T02:44:10Z"},"accession":"S-EPMC2253262","cross_references":{"pubmed":["15840828"],"doi":["10.1110/ps.041256705"]}}