tryptophan-tryptophylquinone and 6-hydroxydopa-quinone

Topics: Amine Oxidase (Copper-Containing); Amino Acid Sequence; Animals; Catalysis; Codon, Terminator; Coenzymes; Copper; Crystallography, X-Ray; Dihydroxyphenylalanine; Dipeptides; Endonucleases; Humans; Indolequinones; Ions; Molecular Sequence Data; Oxidoreductases Acting on CH-NH Group Donors; RNA-Directed DNA Polymerase; Tryptophan

Prior to 1990, redox cofactors were widely believed to be small molecule, dissociable compounds. In the past 10 years, however, four novel redox cofactors have been discovered, each of which is derived from posttranslational modification of specific amino acids within their cognate enzymes. These include topa quinone, found in copper amine oxidases, lysine tyrosyl quinone, found in lysyl oxidase, tryptophan tryptophylquinone, found in methylamine dehydrogenase, and the cysteine-cross-linked tyrosine found in galactose oxidase. The processes by which these cofactors are formed, called biogenesis, is currently a major focus of mechanistic work in this field. In this review, the latest progress toward elucidating the various biogenesis mechanisms is discussed, along with possible linkages between the chemistries involved in catalysis and biogenesis.

Topics: Amino Acid Oxidoreductases; Amino Acids; Coenzymes; Dihydroxyphenylalanine; Galactose Oxidase; Indolequinones; Lysine; Oxidation-Reduction; Quinones; Tryptophan

O-quinone cofactors derived from tyrosine and tryptophan are involved in novel biological reactions that range from oxidative deaminations to free-radical redox reactions. The formation of each of these cofactors appears to involve post-translational modifications of either tyrosine or tryptophan residues. The modifications result in cofactors, such as topaquinone (TPQ), tryptophan tryptophylquinone (TTQ), lysine tyrosylquinone (LTQ) or the copper-complexed cysteinyl-tyrosyl radical from metal-catalyzed reactions. Pyrroloquinoline quinone (PQQ) appears to be formed from the annulation of peptidyl glutamic acid and tyrosine residues stemming from their modification as components of a precursor peptide substrate. PQQ, a primary focus of this review, has invoked considerable interest because of its presence in foods, antioxidant properties and role as a growth-promoting factor. Although no enzymes in animals have been identified that exclusively utilize PQQ, oral supplementation of PQQ in nanomolar amounts increases the responsiveness of B- and T-cells to mitogens and improves neurologic function and reproductive outcome in rodents. Regarding TPQ and LTQ, a case may be made that the formation of TPQ and LTQ is also influenced by nutritional status, specifically dietary copper. For at least one of the amine oxidases, lysyl oxidase, enzymatic activity correlates directly with copper intake. TPQ and LTQ are generated following the incorporation of copper by a process that involves the two-step oxidation of a specified tyrosyl residue to first peptidyl dopa and then peptidyl topaquinone to generate active enzymes, generally classed as "quinoenzymes." Limited attention is also paid to TTQ and the copper-complexed cysteinyl-tyrosyl radical, cofactors important to fungal and bacterial redox processes.

Topics: Animals; Coenzymes; Dihydroxyphenylalanine; Enzymes; Humans; Indolequinones; Lysine; PQQ Cofactor; Quinolones; Quinones; Tryptophan

Topics: Amino Acids; Animals; Catalysis; Coenzymes; Dihydroxyphenylalanine; Indolequinones; Lysine; Protein Processing, Post-Translational; Quinones; Tryptophan

This review is concerned with the structure and function of the quinoprotein enzymes, sometimes called quinoenzymes. These have prosthetic groups containing quinones, the name thus being analogous to the flavoproteins containing flavin prosthetic groups. Pyrrolo-quinoline quinone (PQQ) is non-covalently attached, whereas tryptophan tryptophylquinone (TTQ), topaquinone (TPQ) and lysine tyrosylquinone (LTQ) are derived from amino acid residues in the backbone of the enzymes. The mechanisms of the quinoproteins are reviewed and related to their recently determined three-dimensional structures. As expected, the quinone structures in the prosthetic groups play important roles in the mechanisms. A second common feature is the presence of a catalytic base (aspartate) at the active site which initiates the reactions by abstracting a proton from the substrate, and it is likely to be involved in multiple reactions in the mechanism. A third common feature of these enzymes is that the first part of the reaction produces a reduced prosthetic group; this part of the mechanism is fairly well understood. This is followed by an oxidative phase involving electron transfer reactions which remain poorly understood. In both types of dehydrogenase (containing PQQ and TTQ), electrons must pass from the reduced prosthetic group to redox centres in a second recipient protein (or protein domain), whereas in amine oxidases (containing TPQ or LTQ), electrons must be transferred to molecular oxygen by way of a redox-active copper ion in the protein.

Topics: Alcohol Oxidoreductases; Amine Oxidase (Copper-Containing); Bacterial Proteins; Binding Sites; Coenzymes; Dihydroxyphenylalanine; Disulfides; Electron Transport; Indolequinones; Lysine; Models, Chemical; Models, Molecular; Molecular Structure; Oxidation-Reduction; Oxidoreductases Acting on CH-NH Group Donors; PQQ Cofactor; Protein-Lysine 6-Oxidase; Quinolones; Quinones; Tryptophan

Recently, two novel quinonoid coenzymes, 2,4,5-trihydroxyphenylalanine quinone (topa quinone; TPQ) and tryptophan tryptophylquinone (TTQ), were identified in copper-containing amine oxidase and methylamine dehydrogenase, respectively. Unlike the formerly known quinonoid coenzyme, pyrroloquinoline quinone (PQQ), which is non-covalently bound to several prokaryotic dehydrogenases and produced through its own biosynthetic pathway, each of TPQ and TTQ is bound covalently to the polypeptide chain as an integral amino acid residue and encoded by a codon for a normal (unmodified) amino acid in the gene. Thus, these coenzymes must be generated through post-translational modification of the precursor amino acid; for TPQ, oxidation of a specific tyrosine occurring in the consensus Asn-Tyr-Asp/Glu sequence, and for TTQ, oxidation of a specific tryptophan and cross-linking with another tryptophan separated by 50 residues in the same polypeptide chain. We recently demonstrated that, using the inactive precursor forms of bacterial copper amine oxidases, TPQ is generated through self-processing of the protein with the participation of the bound copper ions. On the other hand, the absence of a prosthetic metal ion in methylamine dehydrogenase as well as its existence in the periplasm renders TTQ biogenesis more complicated, likely requiring an external enzymatic system(s).

Topics: Amine Oxidase (Copper-Containing); Amino Acid Sequence; Animals; Coenzymes; Dihydroxyphenylalanine; Humans; Indolequinones; Molecular Sequence Data; Oxidoreductases Acting on CH-NH Group Donors; Quinones; Sequence Alignment; Tryptophan

Topics: Amino Acid Sequence; Animals; Coenzymes; Dihydroxyphenylalanine; Indolequinones; Molecular Sequence Data; Oxidation-Reduction; Oxidoreductases Acting on CH-NH Group Donors; PQQ Cofactor; Quinolones; Quinones; Sequence Homology, Amino Acid; Tryptophan

As used today, the word quinoprotein defines three distinct groups of enzymes. Before 1979, the structures of the essential, quinonoid oxidation-reduction cofactors were a mystery for all these enzymes. The first proteins proven to harbor this type prosthetic group are those with noncovalently bound pyrroloquinoline quinone (PQQ). PQQ-containing enzymes can be described as alcohol dehydrogenases, with the exception of a single protein, which is an amine dehydrogenase. More recently, it was discovered that copper-containing amine oxidases contain 6-hydroxydopa quinone, also known as topa quinone (TQ), whereas certain bacterial amine dehydrogenases require 2',4-bitryptophan-6,7-dione (tryptophan tryptophylquinone, TTQ) for activity. These latter two quinones are formed, by unknown processes, from a specific tyrosyl residue for the amine oxidases, and from two widely separate tryptophyl residues in the polypeptide of the amine dehydrogenases.

Topics: Coenzymes; Dihydroxyphenylalanine; Indolequinones; Oxidation-Reduction; PQQ Cofactor; Quinolones; Quinones; Tryptophan

The presently best known and largest group of quinoproteins consists of enzymes using the cofactor 2,7,9-tricarboxy-1H-pyrrolo[2,3-f]quinoline- 4,5-dione (PQQ), a compound having a pyrrole ring fused to a quinoline ring with an o-quinone group in it. Representatives of this group are found among the bacterial, NAD(P)-independent, periplasmic dehydrogenases. Despite their high midpoint redox potential, the overall behaviour of quinoprotein dehydrogenases is similar to that of their counterparts, those using a flavin cofactor or a nicotinamide coenzyme. Apart from an exceptional Gram-positive one, the sole organisms where the presence of PQQ has really been established are Gram-negative bacteria. Evidence for the occurrence of covalently bound PQQ is lacking since it has now been shown that several enzymes previously considered to contain this prosthetic group do not in fact do so. Another group of quinoproteins, consisting of amine oxidoreductases, has a protein chain containing one of the following quinonoid aromatic amino acids: 6-hydroxy-phenylalanine-3,4-dione (TPQ) or 4-(2'-tryptophyl)-tryptophan-6,7-dione (TTQ). There is no doubt that these o-quinones play a role as cofactor, in the case of TPQ in prokaryotic as well as eukaryotic amine oxidases. It appears, therefore, that a novel class of amino-acid-derived cofactors is emerging, ranging from the free radical form of tyrosine and tryptophan to those containing a dicarbonyl group (like the already known pyryvoyl group and the o-quinones here described.

Topics: Coenzymes; Dihydroxyphenylalanine; Enzymes; Gram-Negative Bacteria; Indolequinones; Molecular Conformation; Oxidoreductases; PQQ Cofactor; Protein Conformation; Quinolones; Quinones; Tryptophan

Topics: Amino Acid Sequence; Coenzymes; Copper; Diabetes Mellitus; Dihydroxyphenylalanine; Electron Spin Resonance Spectroscopy; Enzyme Inhibitors; Heart Failure; Humans; Indolequinones; Liver Cirrhosis; Lysine; Menkes Kinky Hair Syndrome; Metalloproteins; Mixed Function Oxygenases; Models, Molecular; Molecular Sequence Data; Oxidation-Reduction; Oxidoreductases Acting on CH-NH Group Donors; PQQ Cofactor; Protein-Lysine 6-Oxidase; Quinolones; Quinones; Semicarbazides; Sequence Homology, Amino Acid; Spectrum Analysis, Raman; Stereoisomerism; Substrate Specificity; Tryptophan

Topics: Coenzymes; Dihydroxyphenylalanine; Indolequinones; Molecular Structure; Oxidoreductases; Paracoccus denitrificans; PQQ Cofactor; Quinolones; Quinones; Tryptophan

Topics: Animals; Coenzymes; Dihydroxyphenylalanine; Humans; Indolequinones; Molecular Structure; PQQ Cofactor; Quinolones; Quinones; Tryptophan