ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P116. Vanadate, a Nonlinear Competetive Inhibitor of Human Prostatic
Acid Phosphatase, Exhibiting Positive Cooperativity in Ligand Binding
E. Luchter-Wasylewska, N. Hutyra, M. Górny
Department of Medical Biochemistry, Jagiellonian University, Collegium Medicum, Kopernika 7, 31-034
Krakow, Krakow, Poland
e-mail: mbwasyle@cyf-kr.edu.pl
Human prostatic acid phosphatase (PAP) catalyses hydrolysis of phosphoesters; it removes phosphate moiety
from phosphoserine (Pser), phosphothreonine (Pthr) and phosphotyrosine (Ptyr) residues. PAP belongs to
regulatory enzymes: it exhibits positive cooperativity in substrate binding; degree of cooperativity grows when
PAP concentration is increased.
PAP was found to be a prostate tumor suppressor. Receptor cErbB2 of the prostate cell was identified as PAP
substrate in vivo: PAP dephosphorylates cErbB2 at tyrosine residues what results in the reduction of its kinase
activity. In advanced prostate cancer cells, the level of PAP is decreased; thus hyperphosphorylation of cErbB2
at tyrosine residues and activation of the downstream extracellular signal-regulated kinase (ERK)/mitogen
activated protein kinase (MAPK) signaling is observed, which results in prostate cancer progresssion.
Studies on inhibition of PAP catalytic activity by vanadate were performed after the cooperative properties of
PAP were stated by us. Vanadate was found to be a nonlinear competitive inhibitor of phenyl phosphate PAPcatalysed
hydrolysis. When inhibitor concentration was increased, the half saturation constant rose, but the
turnover number and the Hill cooperation coefficient remained constant. Thus, sodium vanadate at growing
concentration did not change the cooperativity in substrate bindng exhibited by PAP.
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