Facial triade

Hegg, E. L. and L. Que (1997). The 2-His-l-carboxylate facial triad-An emerging structural motif in mononuclear non-heme iron(II) enzymes. Eur. J. Biochem. 250(3) 625-629. 

Figure 13.19 Reactions catalysed by each of the five families of mononuclear non-haem iron enzymes with a 2-His-l-carboxylate facial triad. Dioxygen is labelled to indicate the fate of each oxygen atom. (From Koehntop et al., 2005. With kind permission of Springer Science and Business Media.)...

The 2-His-l-Carboxylate Facial Triad in Non-Heme Iron Oxygenases 101... 

The number of known or presumed mononuclear, non-heme iron oxygenases and related enzymes continues to grow. This is due to intensive biochemical research and especially based on sequence data derived from genome research projects i.14). For several of these enzymes structural data are available by now from protein crystallography (12-14). In many of the iron oxygenases the iron is facially bound by two histidines and one carboxylate donor, either glutamic acid or aspartic acid. Thus, the term 2-His-l-carboxylate facial triad has been introduced by L. Que Jr. for this motif (19). 

In 2-OG dependent enzymes ferrous iron is bound in the active site by the 2-His-l-carboxyIate facial triad. The carboxylate is either an aspartic acid or a glutamic acid. In the beginning the slightly distorted... 

His-l-carboxylate facial triad. In these ligands the two pyrazol-l-yl... 

Inspired by the 2-His-l-carboxylate facial triad our interest focused on the development of a new facially coordinating tripod ligand which... 

Scheme 2.5 Ligands used to synthesize structural and/or functional models for iron enzymes containing a 2-His-l-carboxylate facial triad (a) R3TACN (TACN = 1,4,7-triazacyclononane) [25] (b) TpR,R [differently substituted hydridotris(pyrazol-l-yl)borates] [27] (c) differently substituted bis(pyrazol-l-yl)acetates [29] (d) differently substituted 3,3-bis(1 -alkylimidazol-2-yl)propionates [30],...

In the area of mononuclear nonheme iron enzymes, x-ray crystal structures are now also available for the catalytic domain of human phenylalanine hydroxylase [18] and naphthalene 1,2-dioxygenase [19]. The mononuclear iron site of phenylalanine hydroxylase resembles the 2-His-l-Asp site of tyrosine hydroxylase, a result anticipated by sequence homology. More interestingly, naphthalene 1,2-dioxygenase, which catalyzes the c/ s-dihydroxylation of arene double bonds in the biodegradation of aromatics, also has a Fe(His)2(Asp) iron site. These two enzymes augment the increasing number of mononuclear nonheme iron enzymes with a common Fe(His)2(carboxylate) facial triad motif [20],... 

Crystal structures for a number of enzymes in this family are now available. Despite the fact that many of these enzymes exhibit minimal sequence identity, they have a conserved Hx(D/E)x H sequence that provides the three endogenous protein ligands of the recurring 2-His-l-carboxylate facial triad motif that binds the high-spin iron(n) center. Three solvent molecules on the opposite face complete the iron coordination sphere. 

Figure 12 shows a generally accepted reaction sequence for these enzymes. O2 can bind trans to any of the facial triad residues forming an adduct that may be described as an iron(III)-superoxide complex as shown in Figure 12d. This superoxide then attacks the electrophilic carbonyl carbon of 2-OG to form iron(IV)-peroxo adduct Figure 12e, which in turn undergoes C-C bond cleavage and subsequent O bond...

K. D. Koehntop, J. P. Emerson, L. Que, Jr., The 2-His-l-carboxylate facial triad A versatile platform for dioxygen activation by mononuclear non-heme iron(Il) enzymes, /. Biol. Inorg. Chem. 10 (2005) 87. 

---