2oz5
From Proteopedia
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|PDB= 2oz5 |SIZE=350|CAPTION= <scene name='initialview01'>2oz5</scene>, resolution 2.000Å | |PDB= 2oz5 |SIZE=350|CAPTION= <scene name='initialview01'>2oz5</scene>, resolution 2.000Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=7XY:{(3-CHLOROBENZYL)[(5-{[(3,3-DIPHENYLPROPYL)AMINO]SULFONYL}-2-THIENYL)METHYL]AMINO}(OXO)ACETIC ACID'>7XY</scene> | + | |LIGAND= <scene name='pdbligand=7XY:{(3-CHLOROBENZYL)[(5-{[(3,3-DIPHENYLPROPYL)AMINO]SULFONYL}-2-THIENYL)METHYL]AMINO}(OXO)ACETIC+ACID'>7XY</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= ptpB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | |GENE= ptpB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oz5 OCA], [http://www.ebi.ac.uk/pdbsum/2oz5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oz5 RCSB]</span> | ||
}} | }} | ||
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[[Category: Grundner, C.]] | [[Category: Grundner, C.]] | ||
[[Category: TBSGC, TB Structural Genomics Consortium.]] | [[Category: TBSGC, TB Structural Genomics Consortium.]] | ||
| - | [[Category: 7XY]] | ||
[[Category: protein tyrosine phosphatase in complex with small molecule inhibitor]] | [[Category: protein tyrosine phosphatase in complex with small molecule inhibitor]] | ||
[[Category: structural genomic]] | [[Category: structural genomic]] | ||
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[[Category: tbsgc]] | [[Category: tbsgc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:25:27 2008'' |
Revision as of 01:25, 31 March 2008
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| , resolution 2.000Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ptpB (Mycobacterium tuberculosis) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB in complex with the specific inhibitor OMTS
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 >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.
About this Structure
2OZ5 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from 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:17437721
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