2gvp | pdb_00002gvp
Solution structure of Human apo Sco1
Structural highlights
Disease[SCO1_HUMAN] Defects in SCO1 are a cause of mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]; also known as cytochrome c oxidase deficiency. A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation. A subset of patients manifest Leigh syndrome.[1] [2] Function[SCO1_HUMAN] Thought to play a role in cellular copper homeostasis, mitochondrial redox signaling or insertion of copper into the active site of COX.[3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe solution structures of apo, Cu(I), and Ni(II) human Sco1 have been determined. The protein passes from an open and conformationally mobile state to a closed and rigid conformation upon metal binding as shown by electrospray ionization MS and NMR data. The metal ligands of Cu(I) are two Cys residues of the CPXXCP motif and a His residue. The latter is suitably located to coordinate the metal anchored by the two Cys residues. The coordination sphere of Ni(II) in solution is completed by another ligand, possibly Asp. Crystals of the Ni(II) derivative were also obtained with the Ni(II) ion bound to the same His residue and to the two oxidized Cys residues of the CPXXCP motif. We propose that the various structures solved here represent the various states of the protein in its functional cycle and that the metal can be bound to the oxidized protein at a certain stage. Although it now seems reasonable that Sco1, which is characterized by a thioredoxin fold, has evolved to bind a metal atom via the di-Cys motif to act as a copper chaperone, the oxidized form of the nickel-bound protein suggests that it may also maintain the thioredoxin function. A hint for the function of human Sco1 from different structures.,Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Mangani S, Martinelli M, Palumaa P, Wang S Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8595-600. Epub 2006 May 30. PMID:16735468[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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