A covalently bound catalytic intermediate in Escherichia coli asparaginase : Crystal structure of a Thr‐89‐Val mutant

@article{Palm1996ACB,
  title={A covalently bound catalytic intermediate in Escherichia coli asparaginase : Crystal structure of a Thr‐89‐Val mutant},
  author={Gottfried J. Palm and Jacek Lubkowski and Christian Derst and S Schleper and Klaus-Heinrich R{\"o}hm and Alexander Wlodawer},
  journal={FEBS Letters},
  year={1996},
  volume={390}
}
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Crystal structure and allosteric regulation of the cytoplasmic Escherichia coli L-asparaginase I.
Structural comparison of Escherichia coli L-asparaginase in two monoclinic space groups.
TLDR
The functional L-asparaginase from Escherichia coli is a homotetramer with a molecular weight of about 142 kDa and the X-ray structure of the enzyme is compared with that of the previously determined crystal form (space group P2(1).
Revealing Escherichia coli type II l-asparaginase active site flexible loop in its open, ligand-free conformation
TLDR
The structure of EcAII wild type in its open conformation is reported for the first time comprising, for at least one protomer, clear electron density for the active site flexible loop (PDB ID: 6YZI).
Geometric considerations support the double‐displacement catalytic mechanism of l‐asparaginase
TLDR
Analysis of the geometry of the interactions indicated that Thr12 (Escherichia coli asparaginase II numbering) is optimally placed to be the primary nucleophile in the most likely scenario utilizing a double‐displacement mechanism, whereas catalysis through a single‐disPLacement mechanism appears to beThe least likely.
Engineering the substrate specificity of Escherichia coli asparaginase II. Selective reduction of glutaminase activity by amino acid replacements at position 248
TLDR
It is found that replacements of A sp248 affected glutamine turnover much more strongly than asparagine hydrolysis in variant N248A, and modeling studies suggested that the selective reduction of glutaminase activity is the result of small conformational changes that affect active‐site residues and catalytically relevant water molecules.
Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase.
TLDR
Kinetic studies show that the loss of the phenolic hydroxyl group at position 25 brought about by the replacement of Y with F strongly impairs kcat without significantly affecting Km.
Three-dimensional structures of L-asparaginase from Erwinia carotovora complexed with aspartate and glutamate.
TLDR
The crystal structures of Erwinia carotovora L-asparaginase complexed with L- aspartate and L-glutamate were determined using the molecular-replacement method and it was found that the arrangement of the ligands practically coincides in all three enzymes.
Do bacterial L-asparaginases utilize a catalytic triad Thr-Tyr-Glu?
Catalytic triads and their relatives.
Structures of two highly homologous bacterial L-asparaginases: a case of enantiomorphic space groups.
TLDR
It is concluded that the observed phenomenon, which is rare, was most likely to have arisen by chance.
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References

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A catalytic role for threonine‐12 of E. coli asparaginase II as established by site‐directed mutagenesis
A left‐handed crossover involved in amidohydrolase catalysis
Crystal structure of Escherichia coli L-asparaginase, an enzyme used in cancer therapy.
TLDR
The crystal structure of Escherichia coli asparaginase II (EC 3.5.1), a drug used for the treatment of acute lymphoblastic leukemia, has been determined and locations for the active sites between the N- and C-terminal domains belonging to different subunits are proposed and postulate a catalytic role for Thr-89.
Probing the role of threonine and serine residues of E. coli asparaginase II by site-specific mutagenesis.
TLDR
Data indicate that the hydroxyl group of Thr12 is directly involved in catalysis, probably by favorably interacting with a transition state or intermediate in Escherichia coli asparaginase II.
A protein catalytic framework with an N-terminal nucleophile is capable of self-activation
TLDR
The name Ntn (N-terminal nucleophile) hydrolases is suggested for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recog-nizable sequence similarity.
Structure of peptide from active site region of Escherichia coli L-asparaginase.
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TLDR
The catalytic mechanism of the 20S proteasome from the archaebacterium Thermoplasma acidophilum has been analyzed by site-directed mutagenesis of the beta subunit and by inhibitor studies, and data show that the nucleophilic attack is mediated by the amino-terminal threonine of processed beta subunits.
L-asparaginase II of Escherichia coli. Studies on the enzymatic mechanism of action.
Abstract The enzymatic mechanism of asparaginase action has been explored using the acyl acceptor, hydroxylamine. Asparaginase catalyzed the synthesis of the hydroxamate from asparagine and more…
Three-dimensional structure of human lysosomal aspartylglucosaminidase
TLDR
The high resolution crystal structure of human lysosomal aspartylglucosaminidase (AGA) has been determined and the catalytically essential residue, the N-terminal threonine of the β-chain is situated in the deep pocket of the funnel-shaped active site.
Structural characterization of Pseudomonas 7A glutaminase-asparaginase.
TLDR
It is suggested that the flexible loops actively participate in the transport of substrate and product molecules through the amidohydrolase active sites and participate in orienting the substrate molecules properly in relation to the catalytic residues.
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