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Deciphering the structural basis of the broad substrate specificity of myo-inositol monophosphatase (IMP) from Cicer arietinum
- Source :
- International Journal of Biological Macromolecules. 151:967-975
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Myo-inositol monophosphatase (IMP) is a crucial enzyme in the inositol biosynthetic pathway that dephosphorylates myo-inositol 1-phosphate and other inositol phosphate derivative compounds to maintain the homeostasis of cellular inositol pool. In our previous research, we have biochemically and functionally characterized IMP enzyme from chickpea (CaIMP), which was able to catalyze diverse substrates. We cloned, overexpressed recombinant CaIMP protein and purified it and further characterized the CaIMP with its three main substrates viz. galactose 1-P, inositol 6-P and fructose 1,6-bisP. Homology model of CaIMP was generated to elucidate the factors contributing to the broad substrate specificity of the protein. The active site of the CaIMP protein was analysed with respect to its interactions with the proposed substrates. Structural features such as, high B-factor and flexible loop regions in the active site, inspired further investigation into the static and dynamic behaviour of the active site of CaIMP protein. The electrostatic biding of each of the key substrates was assessed through molecular docking. Furthermore, molecular dynamics simulations showed that these interactions indeed were stable for extended periods of time under physiological conditions. These experiments conclusively allowed us to establish the primary factors contributing to the promiscuity in substrate binding by CaIMP protein.
- Subjects :
- Protein Conformation
02 engineering and technology
Molecular Dynamics Simulation
Biochemistry
Catalysis
Substrate Specificity
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
Structural Biology
Catalytic Domain
Inositol
Amino Acid Sequence
Homology modeling
Inositol phosphate
Molecular Biology
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Binding Sites
biology
Substrate (chemistry)
Active site
Fructose
General Medicine
021001 nanoscience & nanotechnology
Cicer
Phosphoric Monoester Hydrolases
Enzyme Activation
Molecular Docking Simulation
Kinetics
Enzyme
chemistry
Galactose
biology.protein
0210 nano-technology
Protein Binding
Subjects
Details
- ISSN :
- 01418130
- Volume :
- 151
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Macromolecules
- Accession number :
- edsair.doi.dedup.....25314c27f284282de91b8dd2dc215716
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2019.11.098