Structures of R- and T-state<i>Escherichia coli</i>Aspartokinase III

Kotaka, Masayo; Ren, Jingshan; Lockyer, M.; Hawkins, Alastair R.; Stammers, D.K.

doi:10.1074/jbc.m605886200

Cited by 57 publications

(33 citation statements)

References 45 publications

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“…The representatives from the first four classes of the AAKF transfer the ␥-phosphate of ATP to a carboxylate or carbamate group of the substrates making acylphosphate bonds, whereas the UMPK enzymes phosphorylate a phosphate group of uridilate. The crystal structure of FomA protein confirmed the assignment of FomA to the AAKF because the enzyme exhibits the polypeptide fold found in all members of the AAKF for which crystal structures have been determined: N-acetyl-L-glutamate kinases (32-34), glutamate-5-kinase (35), carbamate kinase (36), aspartokinases (37)(38)(39), and uridylate kinases (40 -43). The search was made by the secondary structure matching data base (44) using FomA coordinates from the FomA⅐MgAMPPNP⅐fosfomycin complex, because that structure is more ordered and complete in comparison to the FomA⅐ DPO one.…”

Section: Resultsmentioning

confidence: 68%

Crystal Structure of Fosfomycin Resistance Kinase FomA from Streptomyces wedmorensis

Pakhomova

Bartlett

Augustus

et al. 2008

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 68%

Crystal Structure of Fosfomycin Resistance Kinase FomA from Streptomyces wedmorensis

Pakhomova

Bartlett

Augustus

et al. 2008

Journal of Biological Chemistry

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“…This confusion originated because of the overall sequence similarity within the AK enzyme family. Lysine-sensitive E. coli AKIII and Arabidopsis AK share about 30% sequence identity with each other (8,9) and have about the same level of sequence identity with the threonine-sensitive mjAK. However, these enzyme families can be distinguished through a comparison of their respective regulatory domain sequences, with the lysine-sensitive AKs having greater than 35% identity with each other and less than 25% identity with the threonine-sensitive mjAK.…”

mentioning

confidence: 99%

“…Each of these regulatory domains is composed of two signature ACT subdomains that are the identifying structural feature of this enzyme superfamily that includes aspartokinases (A), chorismate mutases (C), prephenate dehydrogenases (TyrA, T), and a number of other dehydrogenases, dehydratases, and oxygenases (22). Although there is also high overall structural similarity within the regulatory domains of the three different AKs, the critical latch loop that undergoes rotational rearrangements leading to tetramer formation and the transition from the R-to T-state in the lysine-sensitive AKs consists of a dozen mainly hydrophilic residues (8,9). In mjAK, the same loop is shortened to only four residues and does not appear to play any role in conformational rearrangements.…”

mentioning

confidence: 99%

“…The recently determined structures of the lysine-sensitive monofunctional aspartokinases from Arabidopsis and Escherichia coli have provided some insights into the mechanism of allosteric regulation by lysine (8,9). Lysine binding induces a transition from a dimeric R-state to the tetrameric T-state, resulting in a rearrangement of the catalytic domain that blocks the ATP binding site.…”

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confidence: 99%

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The Structural Basis for Allosteric Inhibition of a Threonine-sensitive Aspartokinase

Liu

Pavlovsky

Viola

2008

Journal of Biological Chemistry

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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.

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“…Based on the crystallographic structures AKs are categorized into three classes. Class I contains the homo-dimeric enzymes from E. coli , Methanococcus jannaschii and A. thaliana with one catalytic domain and two ACT domains per monomer [26], [27], [28]. The dimerization is mediated by the association of the ACT domains.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of Clostridium acetobutylicum aspartate kinase (CaAk): An important allosteric enzyme for amino acids production

Manjasetty

Chance

Burley

et al. 2014

Biotechnology Reports

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Aspartate kinase (AK) is an enzyme which is tightly regulated through feedback control and responsible for the synthesis of 4-phospho-l-aspartate from l-aspartate. This intermediate step is at an important branch point where one path leads to the synthesis of lysine and the other to threonine, methionine and isoleucine. Concerted feedback inhibition of AK is mediated by threonine and lysine and varies between the species. The crystal structure of biotechnologically important Clostridium acetobutylicum aspartate kinase (CaAK; E.C. 2.7.2.4; Mw = 48,030 Da; 437aa; SwissProt: Q97MC0) has been determined to 3 Å resolution. CaAK acquires a protein fold similar to the other known structures of AKs despite the low sequence identity (<30%). It is composed of two domains: an N-terminal catalytic domain (kinase domain) and a C-terminal regulatory domain further comprised of two small domains belonging to the ACT domain family. Pairwise comparison of 12 molecules in the asymmetric unit helped to identify the bending regions which are in the vicinity of ATP binding site involved in domain movements between the catalytic and regulatory domains. All 12 CaAK molecules adopt fully open T-state conformation leading to the formation of three tetramers unique among other similar AK structures. On the basis of comparative structural analysis, we discuss tetramer formation based on the large conformational changes in the catalytic domain associated with the lysine binding at the regulatory domains. The structure described herein is homologous to a target in wide-spread pathogenic (toxin producing) bacteria such as Clostridiumtetani (64% sequence identity) suggesting the potential of the structure solved here to be applied for modeling drug interactions. CaAK structure may serve as a guide to better understand and engineer lysine biosynthesis for the biotechnology industry.

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Structures of R- and T-stateEscherichia coliAspartokinase III

Cited by 57 publications

References 45 publications

Crystal Structure of Fosfomycin Resistance Kinase FomA from Streptomyces wedmorensis

Crystal Structure of Fosfomycin Resistance Kinase FomA from Streptomyces wedmorensis

The Structural Basis for Allosteric Inhibition of a Threonine-sensitive Aspartokinase

Crystal structure of Clostridium acetobutylicum aspartate kinase (CaAk): An important allosteric enzyme for amino acids production

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