Reaction participants Show >> << Hide
- Name help_outline L-histidine Identifier CHEBI:57595 Charge 0 Formula C6H9N3O2 InChIKeyhelp_outline HNDVDQJCIGZPNO-YFKPBYRVSA-N SMILEShelp_outline [NH3+][C@@H](Cc1c[nH]cn1)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 36 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NH4+ Identifier CHEBI:28938 (CAS: 14798-03-9) help_outline Charge 1 Formula H4N InChIKeyhelp_outline QGZKDVFQNNGYKY-UHFFFAOYSA-O SMILEShelp_outline [H][N+]([H])([H])[H] 2D coordinates Mol file for the small molecule Search links Involved in 528 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline trans-urocanate Identifier CHEBI:17771 (Beilstein: 5735282) help_outline Charge -1 Formula C6H5N2O2 InChIKeyhelp_outline LOIYMIARKYCTBW-OWOJBTEDSA-M SMILEShelp_outline [O-]C(=O)\C=C\c1c[nH]cn1 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:21232 | RHEA:21233 | RHEA:21234 | RHEA:21235 | |
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Publications
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Friedel-Crafts-type mechanism for the enzymatic elimination of ammonia from histidine and phenylalanine.
Poppe L., Retey J.
The surprisingly high catalytic activity and selectivity of enzymes stem from their ability to both accelerate the target reaction and suppress competitive reaction pathways that may even be dominant in the absence of enzymes. For example, histidine and phenylalanine ammonia-lyases (HAL and PAL) t ... >> More
The surprisingly high catalytic activity and selectivity of enzymes stem from their ability to both accelerate the target reaction and suppress competitive reaction pathways that may even be dominant in the absence of enzymes. For example, histidine and phenylalanine ammonia-lyases (HAL and PAL) trigger the abstraction of the nonacidic beta protons of these amino acids while leaving the much more acidic ammonium hydrogen atoms untouched. Both ammonia-lyases have a catalytically important electrophilic group, which was believed to be dehydroalanine for 30 years but has now been revealed by X-ray crystallography and UV spectroscopy to be a highly electrophilic 5-methylene-3,5-dihydroimidazol-4-one (MIO) group. Experiments suggest that the reaction is initiated by the electrophilic attack of MIO on the aromatic ring of the substrate. This incomplete Friedel-Crafts-type reaction leads to the activation of a beta proton and its stereospecific abstraction, followed by the elimination of ammonia and regeneration of the MIO group. The plausibility of such a mechanism is supported by a synthetic model. The application of the PAL reaction in the biocatalytic synthesis of enantiomerically pure alpha-amino beta-aryl propionates from aryl acrylates is also discussed. << Less
Angew Chem Int Ed Engl 44:3668-3688(2005) [PubMed] [EuropePMC]
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Characterization of the active site of histidine ammonia-lyase from Pseudomonas putida.
Rother D., Poppe L., Viergutz S., Langer B., Retey J.
Elucidation of the 3D structure of histidine ammonia-lyase (HAL, EC 4.3.1.3) from Pseudomonas putida by X-ray crystallography revealed that the electrophilic prosthetic group at the active site is 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) [Schwede, T.F., Rétey, J., Schulz, G.E. (1999) Bioc ... >> More
Elucidation of the 3D structure of histidine ammonia-lyase (HAL, EC 4.3.1.3) from Pseudomonas putida by X-ray crystallography revealed that the electrophilic prosthetic group at the active site is 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) [Schwede, T.F., Rétey, J., Schulz, G.E. (1999) Biochemistry, 38, 5355-5361]. To evaluate the importance of several amino-acid residues at the active site for substrate binding and catalysis, we mutated the following amino-acid codons in the HAL gene: R283, Y53, Y280, E414, Q277, F329, N195 and H83. Kinetic measurements with the overexpressed mutants showed that all mutations resulted in a decrease of catalytic activity. The mutants R283I, R283K and N195A were approximately 1640, 20 and 1000 times less active, respectively, compared to the single mutant C273A, into which all mutations were introduced. Mutants Y280F, F329A and Q277A exhibited approximately 55, 100 and 125 times lower activity, respectively. The greatest loss of activity shown was in the HAL mutants Y53F, E414Q, H83L and E414A, the last being more than 20 900-fold less active than the single mutant C273A, while H83L was 18 000-fold less active than mutant C273A. We propose that the carboxylate group of E414 plays an important role as a base in catalysis. To investigate a possible participation of active site amino acids in the formation of MIO, we used the chromophore formation upon treatment of HAL with l-cysteine and dioxygen at pH 10.5 as an indicator. All mutants, except F329A showed the formation of a 338-nm chromophore arising from a modified MIO group. The UV difference spectra of HAL mutant F329A with the MIO-free mutant S143A provide evidence for the presence of a MIO group in HAL mutant F329A also. For modelling of the substrate arrangement within the active site and protonation state of MIO, theoretical calculations were performed. << Less