title: Crystal structure of Homo sapiens PTD012 reveals a zinc-containing hydrolase fold.
abstract: The human protein PTD012 is the longer product of an alternatively spliced gene and was described to be localized in the nucleus. The X-ray structure analysis at 1.7 A resolution of PTD012 through SAD phasing reveals a monomeric protein and a novel fold. The shorter splice form was also studied and appears to be unfolded and non-functional. The structure of PTD012 displays an alphabetabetaalpha four-layer topology. A metal ion residing between the central beta-sheets is partially coordinated by three histidine residues. X-ray absorption near-edge structure (XANES) analysis identifies the PTD012-bound ion as Zn(2+). Tetrahedral coordination of the ion is completed by the carboxylate oxygen atom of an acetate molecule taken up from the crystallization buffer. The binding of Zn(2+) to PTD012 is reminiscent of zinc-containing enzymes such as carboxypeptidase, carbonic anhydrase, and beta-lactamase. Biochemical assays failed to demonstrate any of these enzyme activities in PTD012. However, PTD012 exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.
authors.affiliation: Protein Structure Factory, Berlin 12489, Germany.
authors.forename: Babu A
authors.initials: BA
authors.lastname: Manjasetty
authors.forename: Konrad
authors.initials: K
authors.lastname: Büssow
authors.forename: Martin
authors.initials: M
authors.lastname: Fieber-Erdmann
authors.forename: Yvette
authors.initials: Y
authors.lastname: Roske
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.forename: Christoph
authors.initials: C
authors.lastname: Scheich
authors.forename: Frank
authors.initials: F
authors.lastname: Götz
authors.forename: Frank H
authors.initials: FH
authors.lastname: Niesen
authors.forename: Udo
authors.initials: U
authors.lastname: Heinemann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004274:DNA, Recombinant; D004950:Esterases / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D016415:Sequence Alignment; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004274:DNA, Recombinant; D007093:Imidazoles; D006639:Histidine; C029899:imidazole; D006867:Hydrolases; C512529:C11orf54 protein, human; D004950:Esterases; D015032:Zinc; D010100:Oxygen