Artículo

Petruk, A.A.; Labanda, M.S.; Álvarez, R.M.S.; Marti, M.A. "The allosteric modulation of thyroxine-binding globulin affinity is entropy driven" (2013) Biochimica et Biophysica Acta - General Subjects. 1830(6):3570-3577
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Abstract:

Background Thyroxine-binding globulin (TBG) is a non-inhibitory member of the serpin family of proteins whose main structural element is the reactive center loop (RCL), that, upon cleavage by proteases, is inserted into the protein core adopting a β-strand conformation (stressed to relaxed transition, S-to-R). After S-to-R transition thyroxine (T4) affinity decreases. However, crystallographic studies in the presence or absence of the hormone in different states are unable to show significant differences in the structure and interactions of the binding site. Experimental results also suggest the existence of several S states (differing in the number of inserted RCL residues), associated with a differential affinity. Methods To shed light into the molecular basis that regulates T4 affinity according to the degree of RCL insertion in TBG, we performed extended molecular dynamics simulations combined with several thermodynamic analysis of the T4 binding to TBG in three different S states, and in the R state. Results Our results show that, despite T4 binding in the protein by similar interactions in all states, a good correlation between the degree of RCL insertion and the binding affinity, driven by a change in TBG conformational entropy, was observed. Conclusion TBG allosteric regulation is entropy driven. The presence of multiple S states may allow more efficient T4 release due to protease activity. General significance The presented results are clear examples of how computer simulation methods can reveal the thermodynamic basis of allosteric effects, and provide a general framework for understanding serpin allosteric affinity regulation. © 2013 Elsevier B.V.

Registro:

Documento: Artículo
Título:The allosteric modulation of thyroxine-binding globulin affinity is entropy driven
Autor:Petruk, A.A.; Labanda, M.S.; Álvarez, R.M.S.; Marti, M.A.
Filiación:Instituto Superior de Investigaciones Biológicas (INSIBIO-CONICET), Chacabuco 461, S. M. de Tucumán, Tucumán, T4000ILI, Argentina
Instituto de Química Física, Faculad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, San Lorenzo 456, Tucumán, T4000CAN, Argentina
Departamento de Química Biológica e INQUIMAE-CONICET, Facultad de Ciencias Exactas and Naturales, Universidad de Buenos Aires, Pabellón 2, Buenos Aires C1428EHA, Argentina
Palabras clave:Allostery; Conformational entropy; Generalized Born surface analysis; Molecular dynamics; Serpin family; Thyroxine-binding globulin; proteinase; thyroxine; thyroxine binding globulin; allosterism; article; binding affinity; binding site; complex formation; conformational transition; controlled study; entropy; enzyme activity; hydrogen bond; molecular dynamics; priority journal; protein binding; protein conformation; protein interaction; protein localization; protein secondary structure; protein stability; protein structure; reaction time; reactive center loop; structure analysis; Allosteric Regulation; Binding Sites; Crystallography, X-Ray; Entropy; Humans; Protein Structure, Secondary; Thyroxine; Thyroxine-Binding Globulin
Año:2013
Volumen:1830
Número:6
Página de inicio:3570
Página de fin:3577
DOI: http://dx.doi.org/10.1016/j.bbagen.2013.02.023
Título revista:Biochimica et Biophysica Acta - General Subjects
Título revista abreviado:Biochim. Biophys. Acta Gen. Subj.
ISSN:03044165
CODEN:BBGSB
CAS:proteinase, 9001-92-7; thyroxine, 7488-70-2; Thyroxine, 7488-70-2; Thyroxine-Binding Globulin
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03044165_v1830_n6_p3570_Petruk

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Citas:

---------- APA ----------
Petruk, A.A., Labanda, M.S., Álvarez, R.M.S. & Marti, M.A. (2013) . The allosteric modulation of thyroxine-binding globulin affinity is entropy driven. Biochimica et Biophysica Acta - General Subjects, 1830(6), 3570-3577.
http://dx.doi.org/10.1016/j.bbagen.2013.02.023
---------- CHICAGO ----------
Petruk, A.A., Labanda, M.S., Álvarez, R.M.S., Marti, M.A. "The allosteric modulation of thyroxine-binding globulin affinity is entropy driven" . Biochimica et Biophysica Acta - General Subjects 1830, no. 6 (2013) : 3570-3577.
http://dx.doi.org/10.1016/j.bbagen.2013.02.023
---------- MLA ----------
Petruk, A.A., Labanda, M.S., Álvarez, R.M.S., Marti, M.A. "The allosteric modulation of thyroxine-binding globulin affinity is entropy driven" . Biochimica et Biophysica Acta - General Subjects, vol. 1830, no. 6, 2013, pp. 3570-3577.
http://dx.doi.org/10.1016/j.bbagen.2013.02.023
---------- VANCOUVER ----------
Petruk, A.A., Labanda, M.S., Álvarez, R.M.S., Marti, M.A. The allosteric modulation of thyroxine-binding globulin affinity is entropy driven. Biochim. Biophys. Acta Gen. Subj. 2013;1830(6):3570-3577.
http://dx.doi.org/10.1016/j.bbagen.2013.02.023