Functional maps of the junctions between interglobular contacts and active sites in glycolytic enzymes -- a comparative analysis of the biochemical and structural data.
BACKGROUND
Oligomers and separate subunits of the glycolytic enzymes often have different catalytic properties. However, spectral data show an apparent lack of significant conformational changes during oligomerization. Since the conformation of an enzyme determines its catalytic properties, the structural mechanism(s) influencing the activity is of considerable interest.


METHODS
Analysis of the spatial structures of the junctions between interglobular contacts and binding sites may give a clue to the mechanism(s) of the activation. In this work, the problem was studied using available structural and biochemical data for the oligomeric enzymes of glycolysis.


RESULTS
Computational analysis of the structures of the junctions has identified three structurally distinct types of junctions: 1. interglobular binding site (2 of 8 enzymes); 2. domain-domain stabilization (5 of 8); and 3. 'sequence overlap' or a local conformational change (all enzymes). Thus the catalytic activity may be influenced through the shifts of the modules of protein structure (types 1, 2) and/or due to a slight change in the local structure (type 3). The more common junctions of types 2 and 3 are well conserved among eukaryotic enzymes, which suggests their biological importance.


CONCLUSIONS
The results suggest that a profound and a complex change in conformation in subunits of an oligomeric enzyme may not be necessary for a significant change in the catalytic properties. The analysis maps the residues important for the junctions and thus for the link between the catalytic activity and the oligomeric state of the enzymes.
Torshin
Ivan Y
IY
Laboratory of Kinetics and Catalysis, Chemical Department of Moscow State University, Moscow, Russia. biotiy@suez.cs.gsu.edu
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D019295:Computational Biology; D004789:Enzyme Activation; D029968:Escherichia coli Proteins / Q000737:chemistry; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry; D006019:Glycolysis; D020035:Holoenzymes / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008121:Nephropidae; D025221:Phosphofructokinases / Q000737:chemistry; D010736:Phosphoglycerate Mutase / Q000737:chemistry; D010751:Phosphopyruvate Hydratase / Q000737:chemistry; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011770:Pyruvate Kinase / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D014305:Triose-Phosphate Isomerase / Q000737:chemistry
D029968:Escherichia coli Proteins; D020035:Holoenzymes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D025221:Phosphofructokinases; D011770:Pyruvate Kinase; D005634:Fructose-Bisphosphate Aldolase; D010751:Phosphopyruvate Hydratase; D014305:Triose-Phosphate Isomerase; D005956:Glucose-6-Phosphate Isomerase; D010736:Phosphoglycerate Mutase