A protein catalytic framework with an N-terminal nucleophile is capable of self-activation

@article{Brannigan1995APC,
  title={A protein catalytic framework with an N-terminal nucleophile is capable of self-activation},
  author={James A. Brannigan and Guy G. Dodson and Helen J. Duggleby and Peter C. E. Moody and Janet L. Smith and Diana R. Tomchick and Alexey G. Murzin},
  journal={Nature},
  year={1995},
  volume={378},
  pages={416-419}
}
THE crystal structures of three amidohydrolases have been determined recently1–3: glutamine PRPP amidotransferase (GAT), penicillin acylase, and the proteasome. These enzymes use the side chain of the amino-terminal residue, incorporated in a β-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon. The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome. Here we show that all three enzymes share an unusual fold in which the… 
Autocatalytic processing of the 20S proteasome
TLDR
It is shown that propeptide processing in the proteasome from Thermoplasma acidophilum is indeed autocatalytic, but is probably intermolecular.
Do N‐terminal nucleophile hydrolases indeed have a single amino acid catalytic center?
TLDR
It is shown that the main chain carbonyl group of GlnB23 forms a hydrogen bond with the leaving group nitrogen, thus influencing the hydrolysis rate, and proposes an interpretation of the complex character of the Hammett plot for the reaction catalyzed by PGA.
Quantum chemical studies of the catalytic mechanism of N-terminal nucleophile hydrolase
TLDR
The quantum chemical calculations showed a crucial role of a specific solvation in decreasing the activation barrier of the reaction by approximately 10 kcal/mol, and it was found that participation of a bridging water molecule in proton shuttling is not necessary for the catalysis.
A Catalytic Mechanism for Cysteine N-Terminal Nucleophile Hydrolases, as Revealed by Free Energy Simulations
TLDR
Free energy simulations in the quantum mechanics/molecular mechanics framework are used to determine the reaction mechanism of amide hydrolysis catalyzed by the prototypical cysteine Ntn-hydrolase, conjugated bile acid hydrolase (CBAH).
A Bound Water Molecule Is Crucial in Initiating Autocatalytic Precursor Activation in an N-terminal Hydrolase*
TLDR
This study provides the first evidence showing that a bound water molecule plays a critical role in initiating intramolecular cleavage in the post-translational modification of the precursor enzyme.
A novel function for the N-terminal nucleophile hydrolase fold demonstrated by the structure of an archaeal inosine monophosphate cyclohydrolase.
TLDR
Comparisons of the two types of IMP cyclohydrolase, PurO and PurH, revealed that there are no similarities in sequence, structure, or the active site architecture, suggesting that they are evolutionarily not related to each other.
The Mechanism of Autocatalytic Activation of Plant-type L-Asparaginases*
TLDR
The crystal structure of an active site mutant of EcAIII is determined, with the catalytic Thr residue substituted by Ala (T179A) leading to a correctly folded but unprocessed molecule, revealing the geometry and molecular environment of the scissile peptide bond.
...
...

References

SHOWING 1-10 OF 27 REFERENCES
Structure of the allosteric regulatory enzyme of purine biosynthesis.
Multi-wavelength anomalous diffraction (MAD) has been used to determine the structure of the regulatory enzyme of de novo synthesis of purine nucleotides, glutamine 5-phosphoribosyl-1-pyrophosphate
Penicillin acylase has a single-amino-acid catalytic centre
TLDR
The analysis shows that the environment of the catalytically active N-terminal serine of the B chain contains no adjacent histidine equivalent to that found in the serine proteases, indicating that this must be an important recognition site for cleavage.
Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution.
The three-dimensional structure of the proteasome from the archaebacterium Thermoplasma acidophilum has been elucidated by x-ray crystallographic analysis by means of isomorphous replacement and
Refined structure of the pyruvoyl-dependent histidine decarboxylase from Lactobacillus 30a.
TLDR
The crystal structure of the pyruvoyl-dependent histidine decarboxylase from Lactobacillus 30a has been refined to an R-value of 0.15 and a description of the overall structure is presented, focusing on secondary structure and subunit association.
Primary structure requirements for the maturation in vivo of penicillin acylase from Escherichia coli ATCC 11105.
TLDR
The two constituent subunits of the enzyme penicillin acylase from Escherichia coli strain ATCC 11105 are derived from a single precursor polypeptide by post-translational processing and the processing pathway in vivo proceeds via an intermediate comprising the alpha subunits plus endopeptide and is thus identical to the pathway which has been determined previously by in vitro analysis.
Structural and evolutionary relationships in lipase mechanism and activation.
TLDR
Crystal structures of a fungal lipase and a human pancreatic lipase which evidently have a divergent evolutionary history are revealed, revealing the stereochemistry at the active site and to identify the positioning of the fatty acid and the glycerol moieties.
Protein splicing: an analysis of the branched intermediate and its resolution by succinimide formation.
TLDR
A succinimide at the C‐terminus of the spliced internal protein is demonstrated, implicating cyclization of asparagine in resolution of the branched intermediate, and an alkali‐labile bond is identified in the brANChed intermediate.
...
...