Crystal structure of Homo sapiens PTD012 reveals a zinc-containing hydrolase fold.
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.
Manjasetty
Babu A
BA
Protein Structure Factory, Berlin 12489, Germany.
Büssow
Konrad
K
Fieber-Erdmann
Martin
M
Roske
Yvette
Y
Gobom
Johan
J
Scheich
Christoph
C
Götz
Frank
F
Niesen
Frank H
FH
Heinemann
Udo
U
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*
D004274:DNA, Recombinant; D007093:Imidazoles; D006639:Histidine; C029899:imidazole; D006867:Hydrolases; C512529:C11orf54 protein, human; D004950:Esterases; D015032:Zinc; D010100:Oxygen