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PDBsum entry 1yts

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Hydrolase PDB id
1yts
Jmol
Contents
Protein chain
278 a.a.
Ligands
SO4 ×2
Waters ×60

References listed in PDB file
Key reference
Title A ligand-Induced conformational change in the yersinia protein tyrosine phosphatase.
Authors H.L.Schubert, E.B.Fauman, J.A.Stuckey, J.E.Dixon, M.A.Saper.
Ref. Protein Sci, 1995, 4, 1904-1913. [DOI no: 10.1002/pro.5560040924]
PubMed id 8528087
Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.
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.
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.
Secondary reference #1
Title Dissecting the catalytic mechanism of protein-Tyrosine phosphatases.
Authors Z.Y.Zhang, Y.Wang, J.E.Dixon.
Ref. Proc Natl Acad Sci U S A, 1994, 91, 1624-1627. [DOI no: 10.1073/pnas.91.5.1624]
PubMed id 8127855
Full text Abstract
Secondary reference #2
Title Crystal structure of yersinia protein tyrosine phosphatase at 2.5 a and the complex with tungstate.
Authors J.A.Stuckey, H.L.Schubert, E.B.Fauman, Z.Y.Zhang, J.E.Dixon, M.A.Saper.
Ref. Nature, 1994, 370, 571-575. [DOI no: 10.1038/370571a0]
PubMed id 8052312
Abstract
Secondary reference #3
Title Expression, Purification, And physicochemical characterization of a recombinant yersinia protein tyrosine phosphatase.
Authors Z.Y.Zhang, J.C.Clemens, H.L.Schubert, J.A.Stuckey, M.W.Fischer, D.M.Hume, M.A.Saper, J.E.Dixon.
Ref. J Biol Chem, 1992, 267, 23759-23766.
PubMed id 1429715
Abstract
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