IMR Press / FBL / Volume 4 / Issue 4 / DOI: 10.2741/torshin1

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Activating oligomerization as intermediate level of signal transduction: analysis of protein-protein contacts and active sites in several glycolytic enzymes
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1 Laboratory of Kinetics and Catalysis, Chair of Physical Chemistry, Chemical Department of Moscow State University, Moscow, 119899, Russia
Front. Biosci. (Landmark Ed) 1999, 4(4), 557–570;
Published: 1 July 1999

A number of enzymes have inactive monomeric and active oligomeric forms. This suggests presence of definite interglobular contact -active site interaction in the enzymes. Although the phenomenon is widely studied in vitro as part of folding process the biological roles of the phenomenon, termed here as "activating oligomerization" are not clearly understood. In this work a procedure for analysis of protein-protein interactions was elaborated. Using spatial structures of several glycolytic enzymes potential role of kinase phosphorylation in regulation of oligomerization of the proteins as well as association of domains in a two-domain protein was assessed. In the enzymes 15-75% of kinase sites (mainly protein kinase C and casein kinase 2 sites) are placed in interglobular contact region(s). Upon being phosphorylated these sites may prevent oligomer formation. In structures of all the enzymes definite evidences of connection between active site and interglobular contact were found. Two structural mechanisms of interglobular contact influence on the active site were proposed. In addition to known mechanism of oligomerization initiated by allosteric metabolites the influence may be also exerted through functional sequence overlap and/or interdomain contact stabilization mechanisms. Implications for regulation of enzyme cellular function(s), signal transduction and metabolic analysis are considered. It is concluded that activating oligomerization may represent an intermediate level of enzyme cellular regulation.

Glycolytic enzymes
Active site
Protein-protein interactions
Kinase phosphorylation
Signal transduction
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