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1q1m

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==Overview==
==Overview==
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Using an NMR-based fragment screening and X-ray crystal structure-based, assembly, starting with millimolar ligands for both the catalytic site and, the second phosphotyrosine binding site, we have identified a, small-molecule inhibitor of protein tyrosine phosphatase 1B with low, micromolar inhibition constant, high selectivity (30-fold) over the highly, homologous T-cell protein tyrosine phosphatase, and good cellular activity, in COS-7 cells.
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Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high selectivity (30-fold) over the highly homologous T-cell protein tyrosine phosphatase, and good cellular activity in COS-7 cells.
==Disease==
==Disease==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Abad-Zapatero, C.]]
[[Category: Abad-Zapatero, C.]]
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[[Category: Ballaron, S.J.]]
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[[Category: Ballaron, S J.]]
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[[Category: Haasch, D.L.]]
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[[Category: Haasch, D L.]]
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[[Category: Hajduk, P.J.]]
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[[Category: Hajduk, P J.]]
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[[Category: Hutchins, C.W.]]
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[[Category: Hutchins, C W.]]
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[[Category: Jirousek, M.R.]]
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[[Category: Jirousek, M R.]]
[[Category: Kaszubska, W.]]
[[Category: Kaszubska, W.]]
[[Category: Liu, G.]]
[[Category: Liu, G.]]
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[[Category: Lubben, T.H.]]
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[[Category: Lubben, T H.]]
[[Category: Pei, Z.]]
[[Category: Pei, Z.]]
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[[Category: Rondinone, C.M.]]
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[[Category: Rondinone, C M.]]
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[[Category: Trevillyan, J.M.]]
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[[Category: Trevillyan, J M.]]
[[Category: Xin, Z.]]
[[Category: Xin, Z.]]
[[Category: Zhao, H.]]
[[Category: Zhao, H.]]
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[[Category: ptp1b]]
[[Category: ptp1b]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:42:18 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:34:57 2008''

Revision as of 12:34, 21 February 2008


1q1m, resolution 2.60Å

Drag the structure with the mouse to rotate

A Highly Efficient Approach to a Selective and Cell Active PTP1B inhibitors

Contents

Overview

Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high selectivity (30-fold) over the highly homologous T-cell protein tyrosine phosphatase, and good cellular activity in COS-7 cells.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Insulin resistance, susceptibility to OMIM:[176885]

About this Structure

1Q1M is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.

Reference

Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor., Liu G, Xin Z, Pei Z, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Zhao H, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR, J Med Chem. 2003 Sep 25;46(20):4232-5. PMID:13678400

Page seeded by OCA on Thu Feb 21 14:34:57 2008

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