Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Bioinformatics and Computational Biology, Baker Center for Bioinformatics and Biological Statistics

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

2015

Journal or Book Title

Biochemistry

Volume

54

Issue

22

First Page

3543

Last Page

3554

DOI

10.1021/acs.biochem.5b00042

Abstract

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 E.coli fructose 1,6-bisphosphate aldolase, E.coli tagatose 1,6-bisphosphate aldolase, and T.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 ones are tetramers. Our analyses suggest that oligomerization not only stabilizes the aldolase structures, showing reduced fluctuations at the subunit interfaces, it further enables 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 re-positioning the enzyme for its next catalytic cycle. These findings suggest that the aldolase global motions are conserved among aldolases having different oligomeric states in order 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.

Comments

This is a manuscript of an article published as Katebi, Ataur R., and Robert L. Jernigan. "Aldolases utilize different oligomeric states to preserve their functional dynamics." Biochemistry 54, no. 22 (2015): 3543-3554. doi:10.1021/acs.biochem.5b00042. Posted with permission.

Copyright Owner

American Chemical Society

Language

en

File Format

application/pdf

Published Version

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