A single mutation in the active site swaps the substrate specificity of N‐acetyl‐L‐ornithine transcarbamylase and N‐succinyl‐L‐ornithine transcarbamylase

@article{Shi2007ASM,
  title={A single mutation in the active site swaps the substrate specificity of N‐acetyl‐L‐ornithine transcarbamylase and N‐succinyl‐L‐ornithine transcarbamylase},
  author={Dashuang Shi and Xiaolin Yu and Juan Cabrera-Luque and Tony Y. Chen and Lauren Roth and Hiroki Morizono and Norma Allewell and Mendel Tuchman},
  journal={Protein Science},
  year={2007},
  volume={16}
}
Transcarbamylases catalyze the transfer of the carbamyl group from carbamyl phosphate (CP) to an amino group of a second substrate such as aspartate, ornithine, or putrescine. Previously, structural determination of a transcarbamylase from Xanthomonas campestris led to the discovery of a novel N‐acetylornithine transcarbamylase (AOTCase) that catalyzes the carbamylation of N‐acetylornithine. Recently, a novel N‐succinylornithine transcarbamylase (SOTCase) from Bacteroides fragilis was… 
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Structures of N‐acetylornithine transcarbamoylase from Xanthomonas campestris complexed with substrates and substrate analogs imply mechanisms for substrate binding and catalysis
TLDR
Crystal structures of the binary complexes of AOTCase with its substrates, carbamoyl phosphate or N‐acetyl‐L‐ornithine (AORN), and the ternary complexes provide insight into the mode of substrate binding and the mechanism of the transcarbamoylation reaction.
Structure and Catalytic Mechanism of a Novel N-Succinyl-l-ornithine Transcarbamylase in Arginine Biosynthesis of Bacteroides fragilis*
TLDR
Comparison of the structures of the new protein with those recently reported for N-acetyl-l-ornithine transcarbamylase indicates that amino acid residue 90 (B. fragilis numbering) plays an important role in conferring substrate specificity in N-succinyl- l-ORNithine versus N-ordithine.
1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphonacetyl-L-ornithine. Catalytic mechanism and correlation with inherited deficiency.
TLDR
The crystal structure of human ornithine transcarbamoylase complexed with the bisubstrate analog N-phosphonacetyl-L-ornithine has been solved at 1.85-A resolution by molecular replacement and enables the role of active site residues in the catalytic mechanism to be critically examined.
1.85-Å Resolution Crystal Structure of Human Ornithine Transcarbamoylase Complexed withN-Phosphonacetyl-l-ornithine
The crystal structure of human ornithine transcarbamoylase complexed with the bisubstrate analogN-phosphonacetyl-l-ornithine has been solved at 1.85-Å resolution by molecular replacement. Deleterious
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TLDR
A model of the three-dimensional structure of OTCase, developed on the basis of its homology to the catalytic subunit of Escherichia coli aspartate transcarbamylase (ATCase), indicates that many mutations that produce severe clinical symptoms are at the active site or buried in the interior of the protein.
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TLDR
A potent inhibitor, N(alpha)-acetyl-N(delta)-phosphonoacetyl -L-ornithine, was synthesized and showed a midpoint of inhibition at approximately 22 nM; this compound may prove to be a useful starting point for designing inhibitors specific to this novel family of transcarbamylases.
Crystal Structure of N-Acetylornithine Transcarbamylase from Xanthomonas campestris
TLDR
This novel protein structure provides a starting point for rational design of specific analogs that may be useful in combating human and plant pathogens that utilize acetylornithine transcarbamylase rather than ornithinetranscarbamymylase.
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In an X-ray diffraction study using the method of multiple isomorphous replacement, the structure of aspartate carbamoyltransferase (EC 2.1.3.2) complexed with the bisubstrate analog
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TLDR
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TLDR
On the basis of the conformational differences of the T and R states of the enzyme, a plausible scheme for catalysis that assumes the ordered binding of substrates and the ordered release of substrate binding is presented.
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