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Molecular modeling and MM-PBSA free energy analysis of endo-1,4-β-xylanase from Ruminococcus albus 8
Dongling Zhan1, Lei Yu2, Hanyong Jin3
1Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, Changchun 130023, China. zdlgale@126.com.
International Journal of Molecular Sciences
|September 30, 2014
Summary
This study models the 3D structure of Ruminococcus albus 8 endo-1,4-β-xylanase (Xyn10A). Molecular dynamics simulations reveal Xyn10A binds substrates more tightly in a skew boat conformation, highlighting subsite -1's importance.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Arabinoxylan is a key cereal cell wall polysaccharide.
- Endo-1,4-β-xylanase (Xyn10A) from Ruminococcus albus 8 degrades arabinoxylan.
- The 3D structure of Xyn10A is currently unknown.
Purpose of the Study:
- To computationally predict the three-dimensional structure of Xyn10A.
- To investigate substrate binding mechanisms and energetics of Xyn10A.
Main Methods:
- Homology modeling based on amino acid sequence.
- 100 ns molecular dynamics (MD) simulations.
- Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) for free energy analysis.
Main Results:
- A reliable 3D model of Xyn10A was generated using homology to Clostridium thermocellum xylanase.
- Xyn10A binds xylotetraose with higher affinity (39.27 kcal·mol⁻¹) in a skew boat (2SO) conformation at subsite -1 compared to the chair (4C1) conformation.
- Subsite -1 is critical for substrate binding, with Asn187 and Trp344 identified as key residues.
Conclusions:
- The study provides a structural model for Xyn10A and insights into its substrate binding.
- Findings suggest a substrate binding pathway involving conformational changes from 4C1 to 2SO at subsite -1.
- This knowledge can guide future protein engineering efforts to enhance Xyn10A performance.
