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Molecular modeling of an active loop structure in lysozyme. Sequence effects or crystal packing?
1Unité d'Immunologie Structurale, Institut Pasteur, Paris, France. rmaroun@pasteur.fr
Journal of Biomolecular Structure & Dynamics
|April 27, 1999
Summary
Lysozyme loop flexibility differs between hen (HEL) and Japanese quail (JEL) sequences. Crystal structures may not fully represent solution-phase epitopes due to conformational preferences.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Dynamics
Background:
- The Val99-Gly104 loop in lysozyme is crucial for active site function and antibody recognition.
- Lysozyme loop conformations vary, with hen lysozyme (HEL) favoring proximal and Japanese quail lysozyme (JEL) favoring distal orientations relative to the active site.
Purpose of the Study:
- To investigate sequence-specific conformational preferences of the lysozyme Val99-Gly104 loop.
- To differentiate sequence effects from crystal packing artifacts on loop conformation.
- To assess the relative conformational free energies of different loop states.
Main Methods:
- Computational modeling and refinement of lysozyme loop conformations.
- Estimation of relative conformational free energies.
- Analysis of existing structural data under varying environmental conditions.
Main Results:
- The 99-104 segment exhibits greater flexibility in HEL than in JEL sequences when unconstrained.
- JEL sequences favor distal loop conformations, while HEL sequences span proximal and distal states.
- Epitope structures observed in crystals may not be conserved in solution for JEL.
Conclusions:
- Sequence dictates distinct conformational preferences for the lysozyme loop, impacting epitope stability.
- The JEL loop requires significant energy to transition from distal to proximal conformations.
- Environmental factors like humidity, temperature, and pressure have negligible effects on loop conformation.