2J0X

CRYSTAL STRUCTURE OF E. COLI ASPARTOKINASE III IN COMPLEX WITH LYSINE AND ASPARTATE (T-STATE)

Summary for 2J0X

• Entry DOI: 10.2210/pdb2j0x/pdb
• Related: 1OHI 2J0W
• Descriptor: LYSINE-SENSITIVE ASPARTOKINASE 3, ASPARTIC ACID, LYSINE, ... (5 entities in total)
• Functional Keywords: feedback inhibition, allosteric regulation, aspartokinase, aspartate pathway, lysine biosynthesis, lysine, kinase, act domain, transferase, amino acid biosynthesis, amino-acid biosynthesis
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 2
• Total formula weight: 97681.40

Authors

Kotaka, M.,Ren, J.,Lockyer, M.,Hawkins, A.R.,Stammers, D.K. (deposition date: 2006-08-07, release date: 2006-08-10, Last modification date: 2024-05-01)

Primary citation

Kotaka, M.,Ren, J.,Lockyer, M.,Hawkins, A.R.,Stammers, D.K.
Structures of R- and T-State Escherichia Coli Aspartokinase III: Mechanisms of the Allosteric Transition and Inhibition by Lysine.
J.Biol.Chem., 281:31544-, 2006

PubMed Abstract: 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 ACT1 domain in R-state AKIII instigates a series of changes that release a "latch", the beta15-alphaK 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.

PubMed: 16905770
DOI: 10.1074/JBC.M605886200

Experimental method

X-RAY DIFFRACTION (2.8 Å)