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Volume 7, Issue 1 (Suppl) J Biotechnol Biomater
ISSN: 2155-952X JBTBM, an open access journal
Enzymology & Mol. Biology 2017
Biotechnology Congress 2017
March 20-21, 2017
Page 32
Notes:
conferenceseries.com
March 20-21, 2017 Rome, Italy
&
15th World Congress on
2nd International Conference on
Biotechnology And Biotech Industries Meet
Enzymology and Molecular Biology
Inhibition of protein tyrosine phosphatase-1B in vitro and in vivo
Alarge number of studies on protein tyrosine phosphatases (PTPases) have been directed towards drug design for
therapeutic intervention because of their critical roles in homeostasis and disorders of metabolism. In contrast to protein
tyrosine kinases, virtually all inhibitors tested against PTPases exhibit only competitive behavior because of their consensus,
active site sequence H/V-C-X 5-R-S/T, a condition leading to low specificity. Having identified protein tyrosine phosphatase-
1B (PTP1B) as the target enzyme of the vanadyl (VO2+) chelate bis(acetylacetonato)oxidovanadium(IV) [VO(acac)2] in
cultured 3T3-L1 adipocytes, we have investigated the basis of inhibition by the VO2+-chelate through steady-state, kinetic
investigations of the recombinant human enzyme (residues 1-321). Our results differ from investigations by others because
we compared the influence of the chelate in the presence of the synthetic substrate p-Nitrophenylphosphate (pNPP) and the
phosphotyrosine-containing undecapeptide DADEpYLIPQQG mimicking residues 988-998 of the epidermal growth factor
receptor, a physiologically relevant substrate. We also compared the inhibitory behavior of VO(acac)2 to that of two other
VO2+-chelates similarly known for their capacity to enhance cellular uptake of glucose as insulin mimetics. The results indicate
that VO (acac)2 acts as a classical uncompetitive inhibitor in the presence of DADEpYLIPQQG but exhibits only apparent
competitive inhibition with pNPP as substrate because uncompetitive inhibitors are more potent pharmacologically than
competitive inhibitors, structural characterization of the site of uncompetitive binding of VO(acac)2 to PTP1B may provide a
new approach to design of inhibitors of high specificity for therapeutic purposes.
Biography
Marvin W. Makinen is Professor in the Department of Biochemistry and Molecular Biology in The University of Chicago, USAand has served as chairman of the department
from 1988 to 1993. He is also a founding member of the Human Rights Board at the university. He did his D.Phil., in the year 1976 in Molecular Biophysics at Oxford Univer-
sity, U.K. Over the past 40 years at The University of Chicago, research in the Makinen lab has been directed towards the structural basis of action of metalloenzymes and
the application of magnetic resonance methods to characterize active site structure and stereochemical relationships of substrates to active site residues in true reaction
intermediates. More recent studies have been carried out to identify the target enzymes of metal -chelates that enhance the cellular uptake of glucose. Because some
metal-chelates are associated with the capacity to enhance preferential uptake of glucose into xenograft tumors in small laboratory animal models, present research has
been directed towards testing their potential as pharmacologic reagents to increase sensitivity of detection of malignant lesions by PET imaging.
Marvin WMakinen
The University of Chicago, USA
Marvin W Makinen, J Biotechnol Biomater 2017, 7:1(Suppl)