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Title
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Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate.
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Authors
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J.A.Stuckey,
H.L.Schubert,
E.B.Fauman,
Z.Y.Zhang,
J.E.Dixon,
M.A.Saper.
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Ref.
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Nature, 1994,
370,
571-575.
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PubMed id
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Abstract
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Protein tyrosine phosphatases (PTPases) and kinases coregulate the critical
levels of phosphorylation necessary for intracellular signalling, cell growth
and differentiation. Yersinia, the causative bacteria of the bubonic plague and
other enteric diseases, secrete an active PTPase, Yop51, that enters and
suppresses host immune cells. Though the catalytic domain is only approximately
20% identical to human PTP1B, the Yersinia PTPase contains all of the invariant
residues present in eukaryotic PTPases, including the nucleophilic Cys 403 which
forms a phosphocysteine intermediate during catalysis. We present here
structures of the unliganded (2.5 A resolution) and tungstate-bound (2.6 A)
crystal forms which reveal that Cys 403 is positioned at the centre of a
distinctive phosphate-binding loop. This loop is at the hub of several
hydrogen-bond arrays that not only stabilize a bound oxyanion, but may activate
Cys 403 as a reactive thiolate. Binding of tungstate triggers a conformational
change that traps the oxyanion and swings Asp 356, an important catalytic
residue, by approximately 6 A into the active site. The same anion-binding loop
in PTPases is also found in the enzyme rhodanese.
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