Lysyl tyrosylquinone

Tryptophan tryptophanylquinone (TTQ). This recently discovered quinone cofactor is similar to the lysyl tyrosylquinone but is formed from two trypto-phanyl side chains.466 It has been found in methyl-amine dehydrogenase from methylotrophic gramnegative bacteria467-469 and also in a bacterial aromatic amine dehydrogenase.470... 

Lysine tyrosylquinone (LTQ). Another copper amine oxidase, lysyl oxidase, which oxidizes side chains of lysine in collagen and elastin (Eq. 8-8) contains a cofactor that has been identified as having a lysyl group of a different segment of the protein in place of the - OH in the 2 position of topaquinone.465 Lysyl oxidase plays an essential role in the crosslinking of collagen and elastin. 

Wang, S. X., Nakamura, N., Klinman, J. P., and Sanders-Loehr, J., 1997, Characterization of the native lysine tyrosylquinone cofactor in lysyl oxidase by resoance Raman, J. Biol. Chem. 272 28841928844. 

In a recent paper, we have documented in detail the isolation and characterization of an active site, cofactor-containing peptide from bovine aorta LO (13). Investigation of this peptide by a combination of Edman sequencing, mass spectrometry and resonance Raman spectroscopy indicates a type of quino-cofactor, previously undescribed, which is derived from the crosslinking of a modified tyrosine to the e-amino group of a lysyl side chain (13). This new cofactor is designated as lysine tyrosylquinone (LTQ, structure shown as 3). 

The copper metalloenzymes are involved in oxygen-using reactions. These enzymes include cytochrome c oxidase (respiratory chain), lysyl oxidase (collagen synthesis), and dopamine [3-hydroxylase (neurotransmitter synthesis). Lysyl oxidase is a small protein with a molecular weight of 32 kDa. This enzyme contains an unusual modification, namely cross-linking between two different parts of its polypeptide chain. The cross-linked region consists of a structure called lysine tyrosylquinone (Klinman, 1996). Two amino acids are involved in this cross-linked structure, and these are Lys 314 and Tyr 349. Lysine tyrosylquinone is used as a cofactor and is necessary for the catalytic activity of the enzyme. Other copper metalloenzymes contain a related cofactor, namely 2,4,5-tiihydrox5q5henylalanine (topaquinone, TPQ). Serum amino oxidase is a copper metalloenzyme that contains TPQ. TPQ consists of a modified residue of phenylalanine. The copper in the active site of the enzyme occurs immediately adjacent to the TPQ cofactor. 

Lysine tyrosylquinone (LTQ) (Figure 3) is the protein-derived cofactor of mammalian lysyl oxidase, an important enzyme in the metabolism of connective tissue. Lysyl oxidase catalyzes the posttranslational modification of elastin and collagen. It oxidizes selected peptidyl lysine residues to peptidyl a-aminoadipic -semialdehyde residues. This initiates formation of the covalent cross-linkages that insolubilize these extracellular proteins. This enzyme also contains copper as a second prosthetic group. 

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