1ND5: Crystal Structures Of Human Prostatic Acid Phosphatase In Complex With A Phosphate Ion And Alpha-Benzylaminobenzylphosphonic Acid Update The Mechanistic Picture And Offer New Insights Into Inhibitor Design

The X-ray crystal structure of human prostatic acid phosphatase (PAP) in complex with a phosphate ion has been determined at 2.4 A resolution. This structure offers a snapshot of the final intermediate in the catalytic mechanism and does not support the role of Asp 258 as a proton donor in catalysis. A total of eight hydrogen bonds serve to strongly bind the phosphate ion within the active site. Bound PEG molecules from the crystallization matrix have allowed the identification of a channel within the molecule that likely plays a role in molecular recognition and in macromolecular substrate selectivity. Additionally, the structure of PAP in complex with a phosphate derivative, alpha-benzylaminobenzylphosphonic acid, a potent inhibitor (IC(50) = 4 nM), has been determined to 2.9 A resolution. This structure gives new insight into the determinants of binding hydrophobic ligands within the active site and allows us to explain PAP's preference for aromatic substrates.
PDB ID: 1ND5Download
MMDB ID: 21542
PDB Deposition Date: 2002/12/7
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 1ND5: trimeric; determined by author
Molecular Components in 1ND5
Label Count Molecule
Proteins (3 molecules)
Prostatic Acid Phosphatase(Gene symbol: ACPP)
Molecule annotation
Chemicals (18 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB