1nwl

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{{STRUCTURE_1nwl| PDB=1nwl | SCENE= }}
{{STRUCTURE_1nwl| PDB=1nwl | SCENE= }}
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'''Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic'''
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===Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic===
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==Overview==
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Protein tyrosine phosphatases play important roles in many signaling cascades involved in human disease. The identification of druglike inhibitors for these targets is a major challenge, and the discovery of suitable phosphotyrosine (pY) mimetics remains one of the key difficulties. Here we describe an extension of tethering technology, "breakaway tethering", which is ideally suited for discovering such new chemical entities. The approach involves first irreversibly modifying a protein with an extender that contains both a masked thiol and a known pY mimetic. The extender is then cleaved to release the pY mimetic, unmasking the thiol. The resulting protein is screened against a library of disulfide-containing small molecule fragments; any molecules with inherent affinity for the pY binding site will preferentially form disulfides with the extender, allowing for their identification by mass spectrometry. The ability to start from a known substrate mimimizes perturbation of protein structure and increases the opportunity to probe the active site using tethering. We applied this approach to the anti-diabetic protein PTP1B to discover a pY mimetic which belongs to a new molecular class and which binds in a novel fashion.
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==Disease==
==Disease==
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[[Category: Waight, A.]]
[[Category: Waight, A.]]
[[Category: Protein-small molecule inhibitor complex]]
[[Category: Protein-small molecule inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:38:00 2008''

Revision as of 04:38, 29 July 2008

Image:1nwl.png

Template:STRUCTURE 1nwl

Contents

Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic

Template:ABSTRACT PUBMED 12733877

Disease

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

About this Structure

1NWL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Discovery of a new phosphotyrosine mimetic for PTP1B using breakaway tethering., Erlanson DA, McDowell RS, He MM, Randal M, Simmons RL, Kung J, Waight A, Hansen SK, J Am Chem Soc. 2003 May 14;125(19):5602-3. PMID:12733877

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