title: Crystal structure of Cu / Zn superoxide dismutase from Taenia solium reveals metal-mediated self-assembly.
abstract: Taenia solium is the cestode responsible for porcine and human cysticercosis. The ability of this parasite to establish itself in the host is related to its evasion of the immune response and its antioxidant defence system. The latter includes enzymes such as cytosolic Cu/Zn superoxide dismutase. In this article, we describe the crystal structure of a recombinant T. solium Cu/Zn superoxide dismutase, representing the first structure of a protein from this organism. This enzyme shows a different charge distribution at the entrance of the active channel when compared with human Cu/Zn superoxide dismutase, giving it interesting properties that may allow the design of specific inhibitors against this cestode. The overall topology is similar to other superoxide dismutase structures; however, there are several His and Glu residues on the surface of the protein that coordinate metal ions both intra- and intermolecularly. Interestingly, one of these ions, located on the β2 strand, establishes a metal-mediated intermolecular β-β interaction, including a symmetry-related molecule. The factors responsible for the abnormal protein-protein interactions that lead to oligomerization are still unknown; however, high metal levels have been implicated in these phenomena, but exactly how they are involved remains unclear. The present results suggest that this structure could be useful as a model to explain an alternative mechanism of protein aggregation commonly observed in insoluble fibrillar deposits.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, México, DF, México. hersan@servidor.unam.mx
authors.forename: Alejandra
authors.initials: A
authors.lastname: Hernández-Santoyo
authors.forename: Abraham
authors.initials: A
authors.lastname: Landa
authors.forename: Edith
authors.initials: E
authors.lastname: González-Mondragón
authors.forename: Martha
authors.initials: M
authors.lastname: Pedraza-Escalona
authors.forename: Ricardo
authors.initials: R
authors.lastname: Parra-Unda
authors.forename: Adela
authors.initials: A
authors.lastname: Rodríguez-Romero
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D003300:Copper / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004795:Enzyme Stability; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020035:Holoenzymes / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D008667:Metalloproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009391:Nephelometry and Turbidimetry; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties; D041201:Taenia solium / Q000201:enzymology*; D015032:Zinc / Q000378:metabolism*
chemical_list: D015801:Helminth Proteins; D020035:Holoenzymes; D008667:Metalloproteins; D011994:Recombinant Proteins; D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc