142A-143S-144G forming 4-methylidene-imidazole-5-one (MIO)
Biostereochemistry of histidine metabolism. II. The steric course of ammonia elimation from L-histidine.
Effects of estrogen, glucocorticoid, glucagon, and adenosine 3':5'-monophosphate on catalytic activity, amount, and rate of de novo synthesis of hepatic histidase.
Presence and quantity of dehydroalanine in histidine ammonia-lyase from Pseudomonas putida.
Identification of Ser143 as the site of modification in the active site of histidine ammonia-lyase.
Purification and characterization of Pseudomonas putida histidine ammonia-lyase expressed in Escherichia coli.
Ser-143 is an essential active site residue in histidine ammonia-lyase of Pseudomonas putida.
Identification of serine-143 as the most likely precursor of dehydroalanine in the active site of histidine ammonia-lyase. A study of the overexpressed enzyme by site-directed mutagenesis.
Enzymatic catalysis by Friedel-Crafts-type reactions.
Crystallization and preliminary X-ray studies of Pseudomonas putida histidine ammonium-lyase.
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND REVISIONS TO 151 AND 438.
Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile.
Homogenization and crystallization of histidine ammonia-lyase by exchange of a surface cysteine residue.
Methylidene-imidazolone (MIO) from histidine and phenylalanine ammonia-lyase.
Methylidene-imidazolone: a novel electrophile for substrate activation.
Characterization of the active site of histidine ammonia-lyase from Pseudomonas putida.
Computational analysis of the autocatalytic posttranslational cyclization observed in histidine ammonia-lyase. A comparison with green fluorescent protein.
Structures of two histidine ammonia-lyase modifications and implications for the catalytic mechanism.
An active site homology model of phenylalanine ammonia-lyase from Petroselinum crispum.
Autocatalytic peptide cyclization during chain folding of histidine ammonia-lyase.
According to the literature [10], a prosthetic group, 4-methylidene-imidazole-5-one (MIO), which is formed from Ala-Ser-Gly at positions 142-144, makes an electrophile, which will be a target for a nucleophilic attack. The MIO group can be formed by two water elimination steps. At the first step, the nitrogen atom of Gly144 makes an intramolecular nucleophilic attack at the carbonyl group of Ala142, resulting in a cyclization. At the second step, a water is eliminated from the sidechain of Ser143, forming the MIO group. According to the literature [10], [12], [13] & [16], the reaction proceeds as follows: (A) Addition of imidazole ring to double-bond of MIO group: (A1) The CD atom of the substrate imidazole ring makes a nucleophilic attack on the electrophilic methylidene group of the prosthetic MIO group, forming a covalent (single-bonded) intermediate between the substrate histidine and the MIO group. (A2) The MIO group becomes aromatic with the 143-O anion stabilized by the amide of Gly196, whilst the positive charged imidazole is stabilized by the pi-electrons of Phe329. (B) Isomerization (change in the position of double-bond): (B1) Tyr280' from the adjacent chain acts as a general base, by abstracting H(re) proton from the beta-carbon, which is acidified by the positive charge of the imidazole ring. The oxygen atom of Tyr280' is hydrogen-bonded to Glu414, which seems to modulate the catalytic function of Tyr280'. (C) Elimination of amine group from alpha-carbon is accompanied by elimination of imidazole ring from MIO group: (C1) The rearrangement of the MIO group eliminates the ammonia from the alpha-carbon, generating a double-bond between the beta-carbon and the alpha-carbon. The eliminated ammonia is stabilzed by Tyr53/Asn195/Asn313, whilst 143-O anion is stabilized by the amide of Gly196 (see [16]).