Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Radicals in Enzyme Catalysis 251
tyrosine residue, was observed in the X-ray crystal structure of the enzyme, in
which Tyr-272 is cross-linked via a thioether linkage to the side chain of Cys-
228 (see Figure 11.16). Mechanistic studies have indicated that this modiWed
tyrosine cofactor is involved in the enzyme’s catalytic mechanism, which
appears to proceed via a radical mechanism.
A number of oxidases and dehydrogenases have been discovered that contain
novel cofactors containing ortho-quinone oxidised aromatic rings. Collectively
this family of proteins are known as quinoproteins, and the cofactors are
illustrated in Figure 11.16. The cofactor pyrroloquinone (PQQ) is found in
methanol dehydrogenase from Methylobacterium extorquens, which catalyses
the oxidation of methanol to formaldehyde. Methylamine dehydrogenase from
M. extorquens, contains the cofactor tryptophylquinone (TTQ), formed by
oxidative cyclisation of Trp-55 and Trp-106, also in the vicinity of a copper
centre. Finally, the copper-containing amine oxidases, found in bacteria and
yeast, contain 2,4,5-trihydroxyphenylalanine quinone (TPQ), formed by oxidation
of an active site tyrosine residue by the copper centre. Thus, there is a small
family of cofactors in which tyrosine and tryptophan amino acids have been
oxidised to form ortho-quinones by a nearby metal centre. In each case, the
NH
272
Tyr 495 HO 2 C HN
His 496 C O
Cu
O
His 581 OH 2
S
HO 2 C N
N 228 C
O
H
O
PQQ
galactose oxidase
CO 2 H
O
H
N
O
C
O
O
HN
N
H
HO
O
O
NH
C
O
N
H
C
O
TTQ
TPQ
Figure 11.16 Structures of ortho-quinone and oxidised amino acid cofactors.