Journal article
Evaluation of Energetic and Dynamic Coupling Networks in a PDZ Domain Protein
Journal of molecular biology, Vol.364(3), pp.337-351
2006
DOI: 10.1016/j.jmb.2006.08.076
PMID: 17011581
Abstract
A number of computational and experimental studies have identified intramolecular communication “pathways” or “networks” important for transmitting allostery. Here, we have used mutagenesis and NMR relaxation methods to investigate the scope and nature of the communication networks found in the second post-synaptic density-95/discs large/zonula occludens-1 (PDZ) domain of the human protein tyrosine phosphatase 1E protein (hPTP1E) (PDZ2). It was found that most mutations do not have a significant energetic contribution to peptide ligand binding. Three mutants that showed significant changes in binding also displayed context-dependent dynamic effects. Both a mutation at a partially exposed site (H71Y) and a buried core position (I35V) had a limited response in side-chain
2H-based dynamics when compared to wild-type PDZ2. In contrast, a change at a second core position (I20F) that had previously been shown to be part of an energetic and dynamic network, resulted in extensive changes in side-chain dynamics. This response is reminiscent to that seen previously upon peptide ligand binding. These results shed light on the nature of the PDZ2 dynamic network and suggest that position 20 in PDZ2 acts as a “hub” that is energetically and dynamically critical for transmitting changes in dynamics throughout the PDZ domain.
Details
- Title: Subtitle
- Evaluation of Energetic and Dynamic Coupling Networks in a PDZ Domain Protein
- Creators
- Ernesto J Fuentes - Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USASteven A Gilmore - Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USARandall V Mauldin - Department of Biochemistry & Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAAndrew L Lee - Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Resource Type
- Journal article
- Publication Details
- Journal of molecular biology, Vol.364(3), pp.337-351
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.jmb.2006.08.076
- PMID
- 17011581
- ISSN
- 0022-2836
- eISSN
- 1089-8638
- Grant note
- DOI: 10.13039/100000001, name: National Science Foundation, award: MCB-0344354
- Language
- English
- Date published
- 2006
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984025298102771
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