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PDBsum entry 2gi4
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure and ligand interactions of the low molecular weight protein tyrosine phosphatase from campylobacter jejuni.
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Authors
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D.Tolkatchev,
R.Shaykhutdinov,
P.Xu,
J.Plamondon,
D.C.Watson,
N.M.Young,
F.Ni.
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Ref.
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Protein Sci, 2006,
15,
2381-2394.
[DOI no: ]
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PubMed id
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Abstract
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A putative low molecular weight protein tyrosine phosphatase (LMW-PTP) was
identified in the genome sequence of the bacterial pathogen, Campylobacter
jejuni. This novel gene, cj1258, has sequence homology with a distinctive class
of phosphatases widely distributed among prokaryotes and eukaryotes. We report
here the solution structure of Cj1258 established by high-resolution NMR
spectroscopy using NOE-derived distance restraints, hydrogen bond data, and
torsion angle restraints. The three-dimensional structure consists of a central
four-stranded parallel beta-sheet flanked by five alpha-helices, revealing an
overall structural topology similar to those of the eukaryotic LMW-PTPs, such as
human HCPTP-A, bovine BPTP, and Saccharomyces cerevisiae LTP1, and to those of
the bacterial LMW-PTPs MPtpA from Mycobacterium tuberculosis and YwlE from
Bacillus subtilis. The active site of the enzyme is flexible in solution and
readily adapts to the binding of ligands, such as the phosphate ion. An
NMR-based screen was carried out against a number of potential inhibitors and
activators, including phosphonomethylphenylalanine, derivatives of the cinnamic
acid, 2-hydroxy-5-nitrobenzaldehyde, cinnamaldehyde, adenine, and hypoxanthine.
Despite its bacterial origin, both the three-dimensional structure and
ligand-binding properties of Cj1258 suggest that this novel phosphatase may have
functional roles close to those of eukaryotic and mammalian tyrosine
phosphatases. The three-dimensional structure along with mapping of
small-molecule binding will be discussed in the context of developing
high-affinity inhibitors of this novel LMW-PTP.
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