2HPA

STRUCTURAL ORIGINS OF L(+)-TARTRATE INHIBITION OF HUMAN PROSTATIC ACID PHOSPHATASE

Summary for 2HPA

• Entry DOI: 10.2210/pdb2hpa/pdb
• Descriptor: PROTEIN (ACID PHOSPHATASE), alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: acid phosphatase, n-propyltartramate, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 162341.72

Authors

Lacount, M.W.,Handy, G.,Lebioda, L. (deposition date: 1998-09-11, release date: 1998-09-16, Last modification date: 2020-07-29)

Primary citation

LaCount, M.W.,Handy, G.,Lebioda, L.
Structural origins of L(+)-tartrate inhibition of human prostatic acid phosphatase.
J.Biol.Chem., 273:30406-30409, 1998

PubMed Abstract: Acid phosphatase activity in the blood serum is usually separated into tartrate-resistant and tartrate-refractory, which is reported as the prostatic acid phosphatase level. Human prostatic acid phosphatase crystals soaked in N-propyl-L-tartramate were used to collect x-ray diffraction data to 2.9 A resolution under cryogenic conditions. Positive difference electron density, corresponding to the inhibitor, was found. The quality of the electron density maps clearly shows the orientation of the carboxylate and N-propyl-substituted amide groups. The hydroxyl group attached to C3 forms two crucial hydrogen bonds with Arg-79 and His-257. Previous crystallographic studies compiled on the tartrate-rat prostatic acid phosphatase binary complex (Lindqvist, Y., Schneider, G., and Vihko, P. (1993) J. Biol. Chem. 268, 20744-20746) erroneously positioned D-tartrate into the active site. Modeling studies have shown that the C3 hydroxyl group on the D(-)-stereoisomer of tartrate, which does not significantly inhibit prostatic acid phosphatase, does not form strong hydrogen bonds with Arg-79 or His-257. The structure of human prostatic acid phosphatase, noncovalently bound in N-propyl-L-tartramate, is used to develop inhibitors with higher specificity and potency than L(+)-tartrate.

PubMed: 9804805
DOI: 10.1074/jbc.273.46.30406

Experimental method

X-RAY DIFFRACTION (2.9 Å)