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Conformational changes in phosphoglucose isomerase induced by ligand binding
Diana Arsenieva1, Constance J Jeffery
1Laboratory for Molecular Biology, MC567, Department of Biological Sciences, University of Illinois, Chicago, IL 60607, USA.
Journal of Molecular Biology
|October 9, 2002
Summary
Researchers determined the X-ray crystal structure of rabbit phosphoglucose isomerase (PGI) without ligands. This reveals how ligand binding induces conformational changes in the enzyme
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Phosphoglucose isomerase (PGI) is a key enzyme in glycolysis, catalyzing the interconversion of glucose-6-phosphate and fructose-6-phosphate.
- PGI shares identity with other proteins, including autocrine motility factor and neuroleukin, suggesting diverse biological roles.
- Understanding PGI's structure is crucial for elucidating its catalytic mechanism and potential therapeutic applications.
Purpose of the Study:
- To determine the high-resolution X-ray crystal structure of unliganded rabbit phosphoglucose isomerase (rPGI).
- To compare the unliganded structure with previously determined liganded structures to identify conformational changes upon ligand binding.
- To characterize the specific regions and residues involved in ligand-induced conformational adjustments within the rPGI active site.
Main Methods:
- X-ray crystallography was employed to solve the structure of rPGI at 1.8Å resolution.
- Isomorphous phasing was utilized, referencing a previously solved structure of rPGI complexed with 6-phosphogluconate.
- Comparative analysis of the new unliganded structure against existing liganded structures was performed.
Main Results:
- A novel X-ray crystal structure of unliganded rPGI was obtained at 1.8Å resolution.
- Ligand binding was observed to induce an "induced fit" conformational change in specific regions of rPGI (residues 209-215, 245-259, 385-389).
- These conformational changes are localized to the active site pocket and differ from previously described movements involving helix 513-521 during the catalytic cycle.
Conclusions:
- The unliganded rPGI structure provides a baseline for understanding ligand-induced conformational dynamics.
- Specific amino acid regions undergo significant conformational adjustments upon substrate or inhibitor binding.
- These findings enhance our understanding of PGI's catalytic mechanism and allosteric regulation.