3C1M

Cyrstal Structure of threonine-sensitive aspartokinase from Methanococcus jannaschii with MgAMP-PNP and L-aspartate

Summary for 3C1M

• Entry DOI: 10.2210/pdb3c1m/pdb
• Related: 3C1N
• Descriptor: Probable aspartokinase, MAGNESIUM ION, ASPARTIC ACID, ... (6 entities in total)
• Functional Keywords: kinase, allosteric inhibition, threonine-sensitive, act domain, amino-acid biosynthesis, threonine biosynthesis, transferase
• Biological source: Methanocaldococcus jannaschii
• Total number of polymer chains: 4
• Total formula weight: 208759.07

Authors

Liu, X. (deposition date: 2008-01-23, release date: 2008-03-25, Last modification date: 2024-02-21)

Primary citation

Liu, X.,Pavlovsky, A.G.,Viola, R.E.
The Structural Basis for Allosteric Inhibition of a Threonine-sensitive Aspartokinase.
J.Biol.Chem., 283:16216-16225, 2008

PubMed Abstract: The commitment step to the aspartate pathway of amino acid biosynthesis is the phosphorylation of aspartic acid catalyzed by aspartokinase (AK). Most microorganisms and plants have multiple forms of this enzyme, and many of these isofunctional enzymes are subject to feedback regulation by the end products of the pathway. However, the archeal species Methanococcus jannaschii has only a single, monofunctional form of AK. The substrate l-aspartate binds to this recombinant enzyme in two different orientations, providing the first structural evidence supporting the relaxed regiospecificity previously observed with several alternative substrates of Escherichia coli AK ( Angeles, T. S., Hunsley, J. R., and Viola, R. E. (1992) Biochemistry 31, 799-805 ). Binding of the nucleotide substrate triggers significant domain movements that result in a more compact quaternary structure. In contrast, the highly cooperative binding of the allosteric regulator l-threonine to multiple sites on this dimer of dimers leads to an open enzyme structure. A comparison of these structures supports a mechanism for allosteric regulation in which the domain movements induced by threonine binding causes displacement of the substrates from the enzyme, resulting in a relaxed, inactive conformation.

PubMed: 18334478
DOI: 10.1074/jbc.M800760200

Experimental method

X-RAY DIFFRACTION (2.3 Å)