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| {{STRUCTURE_2oz5| PDB=2oz5 | SCENE= }} | | {{STRUCTURE_2oz5| PDB=2oz5 | SCENE= }} |
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| '''Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS'''
| | ===Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS=== |
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| ==Overview==
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| Tyrosine kinases and phosphatases establish the crucial balance of tyrosine phosphorylation in cellular signaling, but creating specific inhibitors of protein Tyr phosphatases (PTPs) remains a challenge. Here, we report the development of a potent, selective inhibitor of Mycobacterium tuberculosis PtpB, a bacterial PTP that is secreted into host cells where it disrupts unidentified signaling pathways. The inhibitor, (oxalylamino-methylene)-thiophene sulfonamide (OMTS), showed an IC(50) of 440 +/- 50 nM and >60-fold specificity for PtpB over six human PTPs. The 2 A resolution crystal structure of PtpB in complex with OMTS revealed a large rearrangement of the enzyme, with some residues shifting >27 A relative to the PtpB:PO(4) complex. Extensive contacts with the catalytic loop provide a potential basis for inhibitor selectivity. Two OMTS molecules bound adjacent to each other, raising the possibility of a second substrate phosphotyrosine binding site in PtpB. The PtpB:OMTS structure provides an unanticipated framework to guide inhibitor improvement.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17437721}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17437721 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17437721}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Tb structural genomics consortium]] | | [[Category: Tb structural genomics consortium]] |
| [[Category: Tbsgc]] | | [[Category: Tbsgc]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:58:28 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:34:06 2008'' |
