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Titolo:
Relation between the flexibility of the WPD loop and the activity of the catalytic domain of protein tyrosine phosphatase SHP-1
Autore:
Yang, J; Niu, TQ; Zhang, AH; Mishra, AK; Zhao, ZZJ; Zhou, GW;
Indirizzi:
Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA UnivMassachusetts Worcester MA USA 01605 ol Med, Worcester, MA 01605 USA Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Dept Med, Nashville, TN 37232 USA
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
fascicolo: 1, volume: 84, anno: 2002,
pagine: 47 - 55
SICI:
0730-2312(2002)84:1<47:RBTFOT>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
CRYSTAL-STRUCTURE; SH2 DOMAINS; SIGNAL-TRANSDUCTION; TRANSITION-STATE; SPECIFICITY; MECHANISM; RECEPTOR; LIGAND; ROLES;
Keywords:
PTPs; SHP-1; catalytic domain; WPD loop; p-NPP; kinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Zhou, GW Univ Massachusetts, Sch Med, Program Mol Med, 373 Plantat St, Worcester, MA 01605 USA Univ Massachusetts 373 Plantat St Worcester MA USA 01605 1605 USA
Citazione:
J. Yang et al., "Relation between the flexibility of the WPD loop and the activity of the catalytic domain of protein tyrosine phosphatase SHP-1", J CELL BIOC, 84(1), 2002, pp. 47-55

Abstract

The conserved WPD loop of protein tyrosine phosphatases play an important role in the catalytic activity and the invariant aspartate residue acts as a general acid/base catalyst in the dephosphorylation reaction. In our previous report, we have demonstrated that the catalytic activities of the PTPsare influenced by the flexibility and stability of the WPD loop in its active "open" conformation [Yang et al., 1998]. Phosphatases with a more flexible WPD loop generally have higher specific activity. In this report, we modify the WPD loop of SHP-1 by alanine-scan mutation of the residues flanking the loop and measure their effects on the catalytic activity of the phosphatase. We show that the S418A, V424A, S426A, E427A, and P428A mutants increase the phosphatase activity, possibly due to the increased flexibility ofthe WPD loop, whereas the L417A, L417G and P425A mutants decrease its phosphatase activity. In addition, we propose that the two-proline residues in the WPD loop (Pro(420) and Pro(425) in SHP-1) work as pivotal points through a conserved hydrophobic network and allows residues between the pivotal points to have maximum flexibility in enhancing the phosphatase activity. Furthermore, our data suggest that the hydrolysis of the phosphoryl-cysteine intermediate, not its formation, is the rate-limiting step with p-nitrophenyl phosphate as the substrate while both the steps are rate-limiting with phosphotyrosine as the substrate. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 18:52:23