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Analyzing Protein Dynamics Using Hydrogen Exchange Mass Spectrometry
Published on: November 29, 2013
La histidina altamente conservada juega un doble papel catalítico en el empalme de proteínas: un mecanismo de
Zhenming Du1, Philip T Shemella, Yangzhong Liu
1Biology Department, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Journal of the American Chemical Society
|July 28, 2009
Resumen
El empalme de proteínas se basa en los residuos de histidina. Este estudio revela una histidina clave.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología Estructural Biología estructural.
Sus antecedentes:
- El empalme de proteínas es un proceso autocatalítico.
- La catálisis ácido-base es crucial para el empalme de proteínas.
- Las histidinas conservadas juegan un papel vital en las proteínas.
Objetivo del estudio:
- Para investigar el papel de la histidina de bloque B conservado en el empalme de proteínas.
- Para determinar los valores de pK (a) del bloque B de histidina en las proteínas precursoras y empalmadas.
- Para dilucidar el mecanismo catalítico de la histidina de bloque B utilizando el modelado computacional.
Principales métodos:
- Determinación de la resonancia magnética nuclear (RMN) pK.
- Modelado de la mecánica cuántica y la mecánica molecular (QM/MM).
- Estudio de las inteinas de ingeniería de Mycobacterium tuberculosis (Mtu) RecA intein.
Principales resultados:
- Se observó un cambio significativo de pK (a) para el bloque B de histidina.
- La histidina del bloque B tiene un pK (a) de 7.3 +/- 0.6 en el precursor y <3.5 en el intein empalmado.
- Los datos QM / MM sugieren un doble papel para la histidina en la catálisis.
Conclusiones:
- La histidina del bloque B actúa como una base general y un ácido general en el empalme de proteínas.
- El desplazamiento observado de la pK (a) explica el papel catalítico y la conservación de la histidina.
- Este mecanismo proporciona una visión de la naturaleza autocatalítica precisa del empalme de proteínas.
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