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Title 

Mutational and kinetic evaluation of conserved His-123 in dual specificity protein-tyrosine phosphatase vaccinia H1-related phosphatase - Participation of Tyr-78 and Thr-73 residues in tuning the orientation of his-123

Authors 

Jin Han KimDeug Young ShinMoon Hi HanMyung Un Choi

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2001

Citation 

Journal of Biological Chemistry, vol. 276, no. 29, pp. 27568-27574

Keywords 

histidinehistoneprotein tyrosine phosphatasethreoninetyrosinevaccinia h1 related protein phosphatasevaccinia virus H1 phosphatase homolog 5kineticsprotein expressionprotein phosphory

Abstract 

Active-site cysteine strategically positioned in the P-loop of protein-tyrosine phosphatases has been suggested to be further stabilized by hydrogen bonding arrays radiating out from the P-loop to neighboring residues. In this work, we investigated the structural role of histidine array in HC(X)5RS motif of the vaccinia H1-related protein phosphatase (VHR), using site-directed mutagenesis in conjunction with an extensive kinetic analysis. Conserved His-123 was mutated along with neighboring residues Tyr-78 and Thr-73. The increased pKa values of active-site Cys-124 found in Y78F and T73A mutants (6.51 and 6.75, respectively) were comparable to those of H123A and H123F mutants. Kinetic evaluation of Y78F and T73A mutants further implicates that the mutations perturb the relative position of Cys-124 within the P-loop. These results imply that Tyr-78 and Thr-73 make up an essential part of the His-123 array and structurally tune the Cys-124 position. Tyr-78 of VHR turns out to be the invariant Tyr reported in several protein-tyrosine phosphatases by a structure-based sequence alignment. Therefore, orientation of the imidazole ring of His-123 by the invariant Tyr-78 is crucial for maintaining the proper position of Cys-124 in the P-loop.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M010526200

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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