1ND6

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

Summary for 1ND6

• Entry DOI: 10.2210/pdb1nd6/pdb
• Related: 1CVI 1ND5 2HPA
• Descriptor: prostatic acid phosphatase, GLYCINE, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: prostatic acid phosphatase, pap, prostate, phosphate, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 169634.16

Authors

Ortlund, E.,LaCount, M.W.,Lebioda, L. (deposition date: 2002-12-07, release date: 2002-12-20, Last modification date: 2024-12-25)

Primary citation

Ortlund, E.,LaCount, M.W.,Lebioda, L.
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
Biochemistry, 42:383-389, 2003

PubMed Abstract: 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.

PubMed: 12525165
DOI: 10.1021/bi0265067

Experimental method

X-RAY DIFFRACTION (2.4 Å)