title: X-ray crystal structure of human calcium-bound S100A1.
abstract: S100A1 is a member of the S100 family of Ca2+-binding proteins and regulates several cellular processes, including those involved in Ca2+signaling and cardiac and skeletal muscle function. In Alzheimer's disease, brain S100A1 is overexpressed and gives rise to disease pathologies, making it a potential therapeutic target. The 2.25 Å resolution crystal structure of Ca2+-S100A1 is solved here and is compared with the structures of other S100 proteins, most notably S100B, which is a highly homologous S100-family member that is implicated in the progression of malignant melanoma. The observed structural differences in S100A1 versus S100B provide insights regarding target protein-binding specificity and for targeting these two S100 proteins in human diseases using structure-based drug-design approaches.
authors.affiliation: Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Zephan
authors.initials: Z
authors.lastname: Melville
authors.affiliation: Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Ehson
authors.initials: E
authors.lastname: Aligholizadeh
authors.affiliation: Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: McKnight
authors.affiliation: Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Weber
authors.affiliation: Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Pozharski
authors.affiliation: Center for Biomolecular Therapeutics, Department of Biochemistry and Molecular Biology, University of Maryland Baltimore, 108 North Greene Street, Baltimore, MD 21201, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002413:Cations, Divalent; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D040681:Structural Homology, Protein
chemical_list: D002413:Cations, Divalent; D020033:Protein Isoforms; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C110294:S100A1 protein; C579160:S100B protein, human; D002118:Calcium
keywords: Alzheimer's disease; S100; S100A1; S100B; calcium-binding proteins; cardiomyopathy; crystal structure