View source for 2oz5

[[Image:2oz5.gif|left|200px]]<br /><applet load="2oz5" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="2oz5, resolution 2.000&Aring;" />
'''Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS'''<br />

==Overview==
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 &gt;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, &gt;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.

==About this Structure==
2OZ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=7XY:'>7XY</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OZ5 OCA]. 

==Reference==
Structural Basis for Selective Inhibition of Mycobacterium tuberculosis Protein Tyrosine Phosphatase PtpB., Grundner C, Perrin D, Hooft van Huijsduijnen R, Swinnen D, Gonzalez J, Gee CL, Wells TN, Alber T, Structure. 2007 Apr;15(4):499-509. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17437721 17437721]
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Alber, T.]]
[[Category: Gee, C.L.]]
[[Category: Grundner, C.]]
[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
[[Category: 7XY]]
[[Category: protein tyrosine phosphatase in complex with small molecule inhibitor]]
[[Category: structural genomics]]
[[Category: tb structural genomics consortium]]
[[Category: tbsgc]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:28:47 2008''