PDBsum entry 1yts

Hydrolase

PDB id: 1yts

Contents

Protein chain

278 a.a. *

Ligands

SO4 ×2

Waters ×60

* Residue conservation analysis

PDB id:

1yts

Name:

Hydrolase

Title:

A ligand-induced conformational change in the yersinia protein tyrosine phosphatase

Structure:

Yersinia protein tyrosine phosphatase. Chain: a. Engineered: yes. Mutation: yes

Source:

Yersinia enterocolitica. Organism_taxid: 630. Strain: w22703. Gene: yop51. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.174

Authors:

H.L.Schubert,J.A.Stuckey,E.B.Fauman,J.E.Dixon,M.A.Saper

Key ref:

H.L.Schubert et al. (1995). A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase. Protein Sci, 4, 1904-1913. PubMed id: 8528087 DOI: 10.1002/pro.5560040924

Date:

07-Apr-95 Release date: 10-Jul-95

Protein chain

P15273  (YOPH_YEREN) -  Tyrosine-protein phosphatase YopH from Yersinia enterocolitica

Seq: 468 a.a.

Struc: 278 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1002/pro.5560040924

Protein Sci 4:1904-1913 (1995)

PubMed id: 8528087

A ligand-induced conformational change in the Yersinia protein tyrosine phosphatase.

H.L.Schubert, E.B.Fauman, J.A.Stuckey, J.E.Dixon, M.A.Saper.

ABSTRACT

Protein tyrosine phosphatases (PTPases) play critical roles in the intracellular signal transduction pathways that regulate cell transformation, growth, and proliferation. The structures of several different PTPases have revealed a conserved active site architecture in which a phosphate-binding loop, together with an invariant arginine, cradle the phosphate of a phosphotyrosine substrate and poise it for nucleophilic attack by an invariant cysteine nucleophile. We previously reported that binding of tungstate to the Yop51 PTPase from Yersinia induced a loop conformational change that moved aspartic acid 356 into the active site, where it can function as a general acid. This is consistent with the aspartic acid donating a proton to the tyrosyl leaving group during the initial hydrolysis step. In this report, using a similar structure of the inactive Cys 403-->Ser mutant of the Yersinia PTPase complexed with sulfate, we detail the structural and functional details of this conformational change. In response to oxyanion binding, small perturbations occur in active site residues, especially Arg 409, and trigger the loop to close. Interestingly, the peptide bond following Asp 356 has flipped to ligate a buried, active site water molecule that also hydrogen bonds to the bound sulfate anion and two invariant glutamines. Loop closure also significantly decreases the solvent accessibility of the bound oxyanion and could effectively shield catalytic intermediates from phosphate acceptors other than water. We speculate that the intrinsic loop flexibility of different PTPases may be related to their catalytic rate and may play a role in the wide range of activities observed within this enzyme family.

Selected figure(s)

Figure 5.
Fig. 5. Conformationalchange in tpe WpDloopmoves Asp 356 into active site and3.6 A romnoxgen of the boundsulfate.The unbound structure (residues 354- 358) is shown in lueand the sulfate-bound structure is shown in yellow with red oxygens and blue nitrogens. The peptide ond between Asp 356 andGln 357 lips between thetwo formingatype 11 fi-turn in theclosed conformation with Gln 57 at the i + 2 position.Thefol- lowing is a list of , shifts between the two forms: Trp 354, 1.9 A; Pro 355,3.8 ; Asp356, 5.0 A; Gln 357, 6.7 A; Thr 358,4.4 A.

Figure 7.
Fig. 7. A watermoleculetrapped in theac- tive site f the sulfate-bound structure bridgestheclosedWpD loop andthebound oxyanion.The ater moleculeiswithin 3.3A of severalresiduesincludingthe .sulfate. istances from the waterare: 3.0 A to sul- ateoxygen 04 thatis nalogous to thescis- ileesterlinkage of phosphotyrosine,2.7 A o sylfateoxygen 02,3.2 A Gln 446 OE 1, .3 A o Gln450 Ne2, and 3.0br. to theam- de of Gln 357 on pD loop. The car- oxylsidechain of.Asp 356 A from he ater and .6 A from 04.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1995, 4, 1904-1913) copyright 1995.

Figures were selected by an automated process.