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Structures of R- and T-state Escherichia coli aspartokinase III: Mechanisms of the allosteric transition and inhibition by lysine

Lookup NU author(s): Professor Alastair Hawkins


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Aspartokinase III (AKIII) from Escherichia coli catalyzes an initial commitment step of the aspartate pathway, giving biosynthesis of certain amino acids including lysine. We report crystal structures of AKIII in the inactive T-state with bound feedback allosteric inhibitor lysine and in the R-state with aspartate and ADP. The structures reveal an unusual configuration for the regulatory ACT domains, in which ACT2 is inserted into ACT1 rather than the expected tandem repeat. Comparison of R- and T-state AKIII indicates that binding of lysine to the regulatory ACT1domain in R-state AKIII instigates a series of changes that release a "latch", the β15-αK loop, from the catalytic domain, which in turn undergoes large rotational rearrangements, promoting tetramer formation and completion of the transition to the T-state. Lysine-induced allosteric transition in AKIII involves both destabilizing the R-state and stabilizing the T-state tetramer. Rearrangement of the catalytic domain blocks the ATP-binding site, which is therefore the structural basis for allosteric inhibition of AKIII by lysine. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Publication metadata

Author(s): Kotaka M, Ren J, Lockyer M, Hawkins AR, Stammers DK

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2006

Volume: 281

Issue: 42

Pages: 31544-31552

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology


DOI: 10.1074/jbc.M605886200

PubMed id: 16905770


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