2j0x

From Proteopedia

Revision as of 15:58, 21 February 2008

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

Overview

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.

About this Structure

2J0X is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Aspartate kinase, with EC number 2.7.2.4 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structures of R- and T-state Escherichia coli aspartokinase III. Mechanisms of the allosteric transition and inhibition by lysine., Kotaka M, Ren J, Lockyer M, Hawkins AR, Stammers DK, J Biol Chem. 2006 Oct 20;281(42):31544-52. Epub 2006 Aug 12. PMID:16905770

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