지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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초록· 키워드
오류제보하기
The activity of cellular signaling proteins modulates cellular processes such as cell growth, immune responses, andneuronal development. Dual specificity phosphatases (DUSPs), which constitute a subfamily of protein tyrosinephosphatases (PTPs), are potential targets for therapeutic development. Recently, allosteric inhibitors of PTPs have shownpromising results with regard to their potency, selectivity and membrane permeability. However, detailed understanding ofthe activity regulation of PTPs is limited. Thus, we determined crystal structures of activity-modulating mutants of DUSP19for which strongly-diffracting crystals are available. One allosteric residue (Ile 187) and two active site residues (Ser 150and Arg 156) were mutated to alanine. High-resolution crystal structure determination and enzyme kinetics analysis of thethree mutants revealed that the mutations resulted in rearrangements in allosteric and local structures. In particular, cavityfillingrearrangements in the I187A mutant were conveyed to the active site, leading to allosteric regulation of enzymeactivity.
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등록된 정보가 없습니다.
참고문헌 (22)
참고문헌 신청
Alonso, A. / 2004 / The minimal essential core of a cysteine-based protein-tyrosine phosphatase revealed by a novel 16-kDa VH1-like phosphatase, VHZ / J Biol Chem 279:35768~35774
Alonso, A. / 2004 / Protein tyrosine phosphatases in the human genome / Cell 117:699~711
Andersen, J. N. / 2001 / Structural and evolutionary relationships among protein tyrosine phosphatase domains / Mol Cell Biol 21:7117~7136
Bermudez, O. / 2010 / The dual-specificity MAP kinase phosphatases : critical roles in development and cancer. Am J Physiol Cell Physiol 299 / Am J Physiol Cell Physiol 299:C189~C202
Blaskovich, M. A. / 2009 / Drug discovery and protein tyrosine phosphatases / Curr Med Chem 16:2095~2176
Alonso, A. / 2004 / Protein tyrosine phosphatases in the human genome / Cell 117:699~711
Andersen, J. N. / 2001 / Structural and evolutionary relationships among protein tyrosine phosphatase domains / Mol Cell Biol 21:7117~7136
Bermudez, O. / 2010 / The dual-specificity MAP kinase phosphatases : critical roles in development and cancer. Am J Physiol Cell Physiol 299 / Am J Physiol Cell Physiol 299:C189~C202
Blaskovich, M. A. / 2009 / Drug discovery and protein tyrosine phosphatases / Curr Med Chem 16:2095~2176
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