Crystal structure of Homo sapiens PTD012 reveals a zinc-containing hydrolase fold

Protein Sci. 2006 Apr;15(4):914-20. doi: 10.1110/ps.052037006. Epub 2006 Mar 7.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • DNA, Recombinant
  • Esterases / metabolism
  • Histidine / chemistry
  • Histidine / metabolism
  • Humans
  • Hydrolases / chemistry*
  • Hydrolases / metabolism
  • Imidazoles / chemistry
  • Imidazoles / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Oxygen / chemistry
  • Oxygen / metabolism
  • Protein Folding*
  • Sequence Alignment
  • Zinc / chemistry
  • Zinc / metabolism*


  • DNA, Recombinant
  • Imidazoles
  • Histidine
  • imidazole
  • Hydrolases
  • C11orf54 protein, human
  • Esterases
  • Zinc
  • Oxygen