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Crystal structure of Homo sapiens PTD012 reveals a zinc‐containing hydrolase fold
Author(s) -
Manjasetty Babu A.,
Büssow Konrad,
FieberErdmann Martin,
Roske Yvette,
Gobom Johan,
Scheich Christoph,
Götz Frank,
Niesen Frank H.,
Heinemann Udo
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.052037006
Subject(s) - hydrolase , chemistry , zinc , carboxylate , histidine , crystallography , carbonic anhydrase , stereochemistry , xanes , enzyme , biochemistry , organic chemistry , physics , quantum mechanics , spectroscopy
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 Å 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 αββα four‐layer topology. A metal ion residing between the central β‐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 β‐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.