Insights into Exogenous Tryptophan-Mediated Allosteric Communication and Helical Transition of TRP Protein for Transcription Regulation.
J Chem Inf Model
; 60(1): 175-191, 2020 01 27.
Article
en En
| MEDLINE
| ID: mdl-31742398
ABSTRACT
In this study, the binding recognition and allosteric mechanism of tryptophan-responsive regulatory protein (TRP)-DNA and bound exogenous tryptophan (Trp) amino acid complexes for transcriptional regulation were explained through the molecular docking, molecular dynamics (MD), free-energy landscape (FEL), binding free energy (molecular mechanics Poisson-Boltzmann surface area, MMPBSA), and protein structural network (PSN) analyses. The domain transition of helix-turn-helix (HTH) and effector binding domain (EBD) of TRP protein is the vital process for allosteric network communication, DNA recognition, and transcription. TRP protein consists of four putative active site pockets (Act1, Act2, Act3, and Act4) with the binding specificity of exogenous Trp amino acid, which modulates the binding energy of TRP-DNA complexes by conferring the specific residual network and internal helical orientation of DNA-binding domain (DBD) for regulatory mechanism. In the TRP-DNA complex, interaction of Arg28 (helix-1) and Arg36 (helix-2) with the DNA molecule plays a vital role in DNA recognition. As a consequence, allosteric induction of exogenous Trp in the Act3 binding site retains the structural integrity and is quite comfortable with DNA major groove; therefore, it produces less binding energy for complex formation and may involve in oligomeric association for transcription regulation. Meanwhile, Trp in the Act1 binding site induces high helical orientation and fluctuations, leading to dissociation of DNA from the TRP protein. The remaining two complexes of Trp with Act2 and Act4 are predicted to partially affect the transcription mechanism. The present study aims to unravel the role of exogenous Trp amino acid in TRP protein for transcriptional regulatory mechanism.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Transcripción Genética
/
Triptófano
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Chem Inf Model
Asunto de la revista:
INFORMATICA MEDICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
India