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Abstract:

Kinetic partitioning between competing routes is present in many biological processes. Here, we propose a methodology to characterize kinetic partitioning through site-directed mutagenesis and apply it to parallel routes for unfolding of the TI I27 protein and for recognition of its target DNA by the human papillomavirus E2 protein. The balance between the two competing reaction routes can be quantified by the partitioning constant Kp. Kp is easily modulated by point mutations, opening the way for the rational design of kinetic partitioning. Conserved wild-type residues strongly favor one of the two competing reactions, suggesting that in these systems there is an evolutionary pressure to shift partitioning towards a certain route. The mutations with the largest effects on partitioning cluster together in space, defining the protein regions most relevant for the modulation of partitioning. Such regions are neither fully coincident with nor strictly segregated from the regions that are important from each competing reaction. We dissected the mutational effects on partitioning into the contributions from each competing route using a new parameter called pi-value. The results suggest how the design of kinetic partitioning may be approached in each case. © The Author 2010. Published by Oxford University Press. All rights reserved.

Registro:

Documento: Artículo
Título:Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding
Autor:Sánchez, I.E.; Ferreiro, D.U.; De Prat Gay, G.
Filiación:Protein Structure-Function and Engineering Laboratory, Fundación Instituto Leloir and IIBBA-CONICET, Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina
Protein Physiology Laboratory, Departamento de Química Biológica, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Palabras clave:kinetic partitioning; point mutation; protein design; protein folding; protein-DNA binding; Biological process; Human papillomavirus; Mutational analysis; Mutational effects; New parameters; Parallel route; Point mutations; protein design; protein-DNA binding; Rational design; Reaction routes; Site directed mutagenesis; Wild types; Design; Protein folding; DNA; article; chemical reaction; gene targeting; kinetics; molecular recognition; mutational analysis; nonhuman; point mutation; priority journal; protein DNA binding; protein folding; quantitative analysis; site directed mutagenesis; wild type; DNA; DNA-Binding Proteins; Humans; Models, Molecular; Muscle Proteins; Mutagenesis, Site-Directed; Oncogene Proteins, Viral; Papillomaviridae; Point Mutation; Protein Binding; Protein Denaturation; Protein Folding; Protein Kinases; Thermodynamics; Human papillomavirus
Año:2011
Volumen:24
Número:1-2
Página de inicio:179
Página de fin:184
DOI: http://dx.doi.org/10.1093/protein/gzq064
Título revista:Protein Engineering, Design and Selection
Título revista abreviado:Protein Eng. Des. Sel.
ISSN:17410126
CODEN:PEDSB
CAS:DNA, 9007-49-2; DNA-Binding Proteins; Muscle Proteins; Oncogene Proteins, Viral; Protein Kinases, 2.7.-; connectin; oncogene protein E2, Human papillomavirus type 1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17410126_v24_n1-2_p179_Sanchez

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Citas:

---------- APA ----------
Sánchez, I.E., Ferreiro, D.U. & De Prat Gay, G. (2011) . Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding. Protein Engineering, Design and Selection, 24(1-2), 179-184.
http://dx.doi.org/10.1093/protein/gzq064
---------- CHICAGO ----------
Sánchez, I.E., Ferreiro, D.U., De Prat Gay, G. "Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding" . Protein Engineering, Design and Selection 24, no. 1-2 (2011) : 179-184.
http://dx.doi.org/10.1093/protein/gzq064
---------- MLA ----------
Sánchez, I.E., Ferreiro, D.U., De Prat Gay, G. "Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding" . Protein Engineering, Design and Selection, vol. 24, no. 1-2, 2011, pp. 179-184.
http://dx.doi.org/10.1093/protein/gzq064
---------- VANCOUVER ----------
Sánchez, I.E., Ferreiro, D.U., De Prat Gay, G. Mutational analysis of kinetic partitioning in protein folding and protein-DNA binding. Protein Eng. Des. Sel. 2011;24(1-2):179-184.
http://dx.doi.org/10.1093/protein/gzq064