Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate

Jeanne A. Stuckey, Heidi L. Schubert, Eric B. Fauman, Zhong-Yin Zhang, Jack E. Dixon, Mark A. Saper

Research output: Contribution to journalArticle

358 Citations (Scopus)

Abstract

PROTEIN tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation1,2. Yersinia, the causative bacteria of the bubonic plague and other enteric diseases, secrete an active PTPase3, Yop51, that enters and suppresses host immune cells4,5. Though the catalytic domain is only ∼20% identical to human PTP1B6, the Yersinia PTPase contains all of the invariant residues present in eukaryotic PTPases7, including the nucleophilic Cys 403 which forms a phosphocysteine intermediate during catalysis3,8-10. We present here structures of the unliganded (2.5 Å resolution) and tungstate-bound (2.6 Å) 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 residue7, by ∼6 Å into the active site. The same anion-binding loop in PTPases is also found in the enzyme rhodanese 11.

Original languageEnglish (US)
Pages (from-to)571-575
Number of pages5
JournalNature
Volume370
Issue number6490
StatePublished - 1994
Externally publishedYes

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Yersinia
Protein Tyrosine Phosphatases
Phosphoric Monoester Hydrolases
Catalytic Domain
Thiosulfate Sulfurtransferase
Plague
Protein-Tyrosine Kinases
Anions
Tyrosine
Hydrogen
Phosphates
Phosphorylation
Bacteria
Enzymes
Growth
tungstate

ASJC Scopus subject areas

  • General

Cite this

Stuckey, J. A., Schubert, H. L., Fauman, E. B., Zhang, Z-Y., Dixon, J. E., & Saper, M. A. (1994). Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate. Nature, 370(6490), 571-575.

Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate. / Stuckey, Jeanne A.; Schubert, Heidi L.; Fauman, Eric B.; Zhang, Zhong-Yin; Dixon, Jack E.; Saper, Mark A.

In: Nature, Vol. 370, No. 6490, 1994, p. 571-575.

Research output: Contribution to journalArticle

Stuckey, JA, Schubert, HL, Fauman, EB, Zhang, Z-Y, Dixon, JE & Saper, MA 1994, 'Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate', Nature, vol. 370, no. 6490, pp. 571-575.
Stuckey JA, Schubert HL, Fauman EB, Zhang Z-Y, Dixon JE, Saper MA. Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate. Nature. 1994;370(6490):571-575.
Stuckey, Jeanne A. ; Schubert, Heidi L. ; Fauman, Eric B. ; Zhang, Zhong-Yin ; Dixon, Jack E. ; Saper, Mark A. / Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate. In: Nature. 1994 ; Vol. 370, No. 6490. pp. 571-575.
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