Acid phosphatase enzyme measurements are regularly performed in connection with the diagnosis and treatment of human prostatic cancer. Besides carcinoma of the prostate, changes in acid phosphatase levels occur in other types of malignant growth, in hairy cell leukemia, in the congenital disorder known as Gaucher's disease, and in a fatal genetic disease characterized by a lack of acid phosphatase. Despite this, little is known about the structural and catalytic properties, and biological role, of the diverse group of enzymes known as acid phosphatases. The present project continues an investigation of the fundamental enzymology of acid phosphatases. The comparative biochemistry and mechanism of action of acid phosphatase enzymes from human prostate, human seminal fluid, bovine liver, human liver and sunflower seed are being examined. Active site peptides are being isolated and partial sequence data are being obtained for them. The structural basis of isoenzyme variation is being determined. Human prostatic and seminal fluid acid phosphatases lacking the usual N-linked carbohydrate residues are being prepared by biosynthesis or by removal of the chains from the homogeneous enzymes using homogeneous peptide N-glycosidases. Extensive sequence data are being obtained for the human prostatic and seminal fluid acid phosphatases. The stereochemistry of hydrolysis and of transfer reactions of phospho substrates are being studied. In addition, the use of the 18O isotope shift in 13C nuclear magnetic resonance spectroscopy is being used to obtain information about oxygen exchange reactions and the mechanisms of enzymatic reactions, including those catalyzed by phosphatases, peptidases and other hydrolases such as asparaginase. The substrate specificity of homogeneous peptide:N-glycosidases will be studied using a series of glycopeptides in which the amino acid and the carbohydrate components are systematically varied. The mechanism of action of the homogeneous peptide N-glycosidases will be studied using NMR to identify potential intermediates and products.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Biochemistry Study Section (BIO)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Purdue University
Schools of Arts and Sciences
West Lafayette
United States
Zip Code
Waheed, Abdul; Hassan, Md Imtaiyaz; Etten, Robert L Van et al. (2008) Human seminal proteinase and prostate-specific antigen are the same protein. J Biosci 33:195-207
Gustafson, Christin L T; Stauffacher, Cynthia V; Hallenga, Klaas et al. (2005) Solution structure of the low-molecular-weight protein tyrosine phosphatase from Tritrichomonas foetus reveals a flexible phosphate binding loop. Protein Sci 14:2515-25
Asthagiri, D; Liu, Tiqing; Noodleman, Louis et al. (2004) On the role of the conserved aspartate in the hydrolysis of the phosphocysteine intermediate of the low molecular weight tyrosine phosphatase. J Am Chem Soc 126:12677-84
Akerud, Tomas; Thulin, Eva; Van Etten, Robert L et al. (2002) Intramolecular dynamics of low molecular weight protein tyrosine phosphatase in monomer-dimer equilibrium studied by NMR: a model for changes in dynamics upon target binding. J Mol Biol 322:137-52
Thomas, Christin L; McKinnon, Evangeline; Granger, Bruce L et al. (2002) Kinetic and spectroscopic studies of Tritrichomonas foetus low-molecular weight phosphotyrosyl phosphatase. Hydrogen bond networks and electrostatic effects. Biochemistry 41:15601-9
Asthagiri, Dilipkumar; Dillet, Valerie; Liu, Tiqing et al. (2002) Density functional study of the mechanism of a tyrosine phosphatase: I. Intermediate formation. J Am Chem Soc 124:10225-35
Waheed, Abdul; Van Etten, Robert L (2002) Protection of prostatic acid phosphatase activity in human serum samples by plasmin inhibitors. Clin Chim Acta 320:127-31
Kikawa, Keith D; Vidale, Derika R; Van Etten, Robert L et al. (2002) Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation. J Biol Chem 277:39274-9
Waheed, A; Van Etten, R L (2001) The biosynthesis of prostate-specific antigen in non prostatic cell lines. Clin Biochem 34:617-21
Wang, S; Stauffacher, C V; Van Etten, R L (2000) Structural and mechanistic basis for the activation of a low-molecular weight protein tyrosine phosphatase by adenine. Biochemistry 39:1234-42

Showing the most recent 10 out of 61 publications