Aldolases Utilize Different Oligomeric States To Preserve Their Functional Dynamics

• Published in: Biochemistry (Easton) Vol. 54; no. 22; pp. 3543 - 3554
• Main Authors: Katebi, Ataur R, Jernigan, Robert L
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.06.2015
• Subjects: Aldehyde-Lyases - chemistry; Aldehyde-Lyases - genetics; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Fructose-Bisphosphate Aldolase - chemistry; Fructose-Bisphosphate Aldolase - genetics; Protein Multimerization; Protein Structure, Quaternary; Protein Structure, Secondary; Thermus - enzymology; Thermus - genetics
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/acs.biochem.5b00042

Aldolases are essential enzymes in the glycolysis pathway and catalyze the reaction cleaving fructose/tagatose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. To determine how the aldolase motions relate to its catalytic process, we studied the dynamics of three different class II aldolase structures through simulations. We employed coarse-grained elastic network normal-mode analyses to investigate the dynamics of Escherichia coli fructose 1,6-bisphosphate aldolase, E. coli tagatose 1,6-bisphosphate aldolase, and Thermus aquaticus fructose 1,6-bisphosphate aldolase and compared their motions in different oligomeric states. The first one is a dimer, and the second and third are tetramers. Our analyses suggest that oligomerization not only stabilizes the aldolase structures, showing fewer fluctuations at the subunit interfaces, but also allows the enzyme to achieve the required dynamics for its functional loops. The essential mobility of these loops in the functional oligomeric states can facilitate the enzymatic mechanism, substrate recruitment in the open state, bringing the catalytic residues into their required configuration in the closed bound state, and moving back to the open state to release the catalytic products and repositioning the enzyme for its next catalytic cycle. These findings suggest that the aldolase global motions are conserved among aldolases having different oligomeric states to preserve its catalytic mechanism. The coarse-grained approaches taken permit an unprecedented view of the changes in the structural dynamics and how these relate to the critical structural stabilities essential for catalysis. The results are supported by experimental findings from many previous studies.