Decarboxylase pyruvoyl enzymes

Figure 14-11 Schematic diagram of the active site of the pyruvoyl enzyme histidine decarboxylase showing key polar interactions between the pyruvoyl group and groups of the inhibitor O-methylhistidine and surrounding enzyme groups. Aspartate 63 appears to form an ion pair with the imidazolium group of the substrate.268 Hydrogen bonds are indicated by dotted lines. See Gallagher et al.269...

Other pyruvate-containing enzymes include aspartate -decarboxylase from Escherichia coli, the enzyme that catalyzes the formation of -alanine for the synthesis of pantothenic acid (Section 12.2.4) proline reductase from Clostridium sticklandiv, phosphatidylserine decarboxylase from E. coli and phenylalanine aminotransferase from Pseudomonas fluorescens. Phospho-pantetheinoyl cysteine decarboxylase, involved in the synthesis of coenzyme A (Section 12.2.1), and S-adenosylmethionine decarboxylase seem to be the only mammalian pyruvoyl enzymes (Snell, 1990). 

Kim AD, Graham DE, Seeholzer SH, Markham GD (2000) S-Adenosylmethionine decarboxylase from the archaeon Methanococcus jannaschii identification of a novel family of pyruvoyl enzymes. J Bacteriol 182 6667-6672... 

Lactobacillus delbrueckii. In 1953, Rodwell suggested that the histidine decarboxylase of Lactobacillus 30a was not dependent upon pyridoxal phosphate (11). Rodwell based his suggestion upon the fact that the organism lost its ability to decarboxylate ornithine but retained high histidine decarboxylase activity when grown in media deficient in pyridoxine. It was not until 1965 that E. E. Snell and coworkers (12) isolated the enzyme and showed that it was, indeed, free of pyridoxal phosphate. Further advances in characterization of the enzyme were made by Riley and Snell (13) and Recsei and Snell (14) who demonstrated the existence of a pyruvoyl residue and the participation of the pyruvoyl residue in histidine catalysis by forming a Schiff base intermediate in a manner similar to pyridoxal phosphate dependent enzymes. Recent studies by Hackert et al. (15) established the subunit structure of the enzyme which is similar to the subunit structure of a pyruvoyl decarboxylase of a Micrococcus species (16). 

Non-pyridoxal Phosphate Dependent. Figure 2 depicts the postulated mechanism for a non-pyridoxal phosphate catal) zed decarboxylation of histidine to histamine involving a pyruvoyl residue instead of pyridoxal -5 - phosphate (20). Histidine decarboxylases from Lactobacillus 30a and a Micrococcus sp. have been shown to contain a covalently bound pyruvoyl residue on the active site. The pyruvoyl group is covalently bound to the amino group of a phenylalanine residue on the enzyme, and is derived from a serine residue (21) of an inactive proenzyme (22). The pyruvoyl residue acts in a manner similar to pyridoxal phosphate in the decarboxylation reaction. 

When 14C-labeled serine was fed to organisms producing histidine decarboxylase, 14C was incorporated into the bound pyruvoyl group (Fig. 14-11). Thus, serine is a precursor of the bound pyruvate. The enzyme is manufactured in the cell as a longer 307-residue proenzyme which associates as hexamers (designated n6). The active enzyme was found to be formed by cleavage of the n chains between Ser 81 and Ser 82 to form 226-residue a chains and 81-residue (3 chains which associate as (aP)6.270/271 The a chains... 

S-Adenosylmethionine decarboxylase is the first enzyme in the biosynthetic pathway to spermidine (Chapter 24). Whether isolated from bacteria, yeast, animals, or other eukaryotes, this enzyme always contains a bound pyruvoyl group.273 274b Both the... 

Although most amino acid decarboxylases use PLP as a cofactor, a number of decarboxylases use covalently bound pyruvate instead (722, 123). The pyruvate-dependent enzyme consists of two types of chains. The pyruvoyl cofactor is formed by the cleavage of a Ser-Ser linkage in a single-chain precursor and is bound as an amide to the N-terminus of one polypeptide chain. 

The elimination of a CO2 molecule from the substrate catalyzed by decarboxylases requires the stabilization of a carbanionic intermediate, a task often performed by enzymatic cofactors. Indeed, decarboxylation reactions on ct-amino acids are catalyzed mainly by PLP-dependent enzymes, with a small fraction of reactions catalyzed by enzymes that use a pyruvoyl cofactor." PLP-dependent decarboxylases are largely widespread among both eukaryotes and prokaryotes where they participate in the biosynthesis of biological amines (e.g., dopamine, histamine, and serotonine) and polyamines. In addition, in prokaryotes, inducible PLP-dependent decarboxylases take part in the regulation of intracellular pH." ... 

Pyruvoyl cofactor is derived from the posttranslational modification of an internal amino acid residue, and it does not equilibrate with exogenous pyruvate. Enzymes that possess this cofactor play an important role in the metabolism of biologically important amines from bacterial and eukaryotic sources. These enzymes include aspartate decarboxylase, arginine decarboxylase," phosphatidylserine decarboxylase, . S-adenosylmethionine decarboxylase, histidine decarboxylase, glycine reductase, and proline reductase. ... 

Figure 1 Structure of the pyruvoyl cofactor in histidine decarboxylase from Lactobacillus 30A. In this enzyme, modification of Ser82 and cleavage of the pro-enzyme between Ser81 and Ser82 yields the pyruvoyl cofactor at the C-terminus of the a-chain, and Ser81 at the N-terminus of the /3-chain of the holoprotein. These residues are displayed as sticks colored gray for carbon, red for oxygen, and blue for nitrogen. The coordinates from PDB entry 1 jen were used to display this structure.

Two enzymes that contain the pyruvoyl cofactor are not decarboxylases D-proline reductase and glycine reductase. These enzymes were originally reported to contain the pyruvate in an ester linkage, but later studies have demonstrated its presence at the N-terminus of one of the subunits linked by the peptide amide bond. In contrast to the pynivoyl-dependent decarboxylases, the site of internal cleavage and modification of these reductases is a cysteine rather than a serine. The mechanism of post-translational biosynthesis of the pyruvoyl cofactor in these enzymes could conceivably proceed through the same mechanism shown in Scheme 1 but with the cysteine sulfur performing the role of the serine oxygen. 

These results suggest that MJ0955 is a hisC and prohahly performs the annotated role in histidine biosynthesis. Thus, the identity of the threonine-phosphate decarboxylase remains to be determined. The possible involvement of a pyruvoyl-dependent enzyme in catalyzing this reaction should be considered. 

Rosenthaler et al. [106] purified histidine decarboxylase from Lactobacillus 30A and demonstrated that there was no pyridoxal phosphate, as had been suggested by Rodwell [107]. Treatment with [ C]phenylhydrazine labeled the protein, but did not if the protein was first reduced with borohydride. Chymotrypsin digestion of the [ C]phenylhydrazone treated enzyme resulted in a labeled fragment identified as A -pyruvoylphenylalanine [100]. Borohydride reduction of the native enzyme resulted in lactate production after hydrolysis. Thus it was established that a pyruvoyl group is covalently bound as an amide to the NH 2-terminal phenylalanine. As is consistent with this proposed mechanism the enzyme is also inhibited by cyanide and by hydroxylamine. The iminium ion predicted by the mechanism above was trapped with borohydride in the presence of substrate and identified [108]. 

Figure 3 compares the proficiencies (kcat/K]v[/kun) of ODCase, several other enzyme decarboxylases [2], and some antibody decarboxylases [3]. The proficiencies of the decarboxylase enzymes, including a variety of amino acid decarboxylases, are nearly equal. Many decarboxylases employ iminium intermediates formed by reaction of an amino acid with a cofactor such as pyruvoyl or pyridoxal, or by reaction of a -keto ester with an active-site lysine residue. These intermediates have been found to be so reactive that the... 

Trip, H., Mulder, N. L., Rattray, R R, Lolkema, J. S. (2011). HdcB, a novel enzyme catalysing maturation of pyruvoyl-dependent histidine decarboxylase. Molecular Microbiology, 79, 861-871. http //dx.doi.Org/10.llll/j.1365-2958.2010.07492.x. 

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