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The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen activation by mononuclear non-heme iron(II) enzymes

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Abstract

General knowledge of dioxygen-activating mononuclear non-heme iron(II) enzymes containing a 2-His-1-carboxylate facial triad has significantly expanded in the last few years, due in large part to the extensive library of crystal structures that is now available. The common structural motif utilized by this enzyme superfamily acts as a platform upon which a wide assortment of substrate transformations are catalyzed. The facial triad binds a divalent metal ion at the active site, which leaves the opposite face of the octahedron available to coordinate a variety of exogenous ligands. The binding of substrate activates the metal center for attack by dioxygen, which is subsequently converted to a high-valent iron intermediate, a formidable oxidizing species. Herein, we summarize crystallographic and mechanistic features of this metalloenzyme superfamily, which has enabled the proposal of a common but flexible pathway for dioxygen activation.

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Notes

  1. A notable exception to this generalization is the case of DAOCS in which α-KG and penicillin were found in recent structures of respective binary complexes to bind in overlapping regions of the active site; it would thus appear that a ternary DAOCS–α-KG–penicillin complex could not form [36].

Abbreviations

α-KG:

α-Ketoglutarate

2,3-CTD:

Catechol 2,3-dioxygenase

4,5-PCD:

Protocatechuate 4,5-dioxygenase

A1:

Deoxyguanidinoproclavaminate

ACCO:

1-Aminocyclopropane-1-carboxylic acid oxidase

ACV:

δ-(L-α-Aminoadipoyl)-L-cysteinyl-D-valine

ANS:

Anthocyanidin synthase

AtsK:

Alkylsulfatase

BH4:

6(R)-L-erythro-5,6,7,8-Tetrahydrobiopterin

BphC:

2,3-Dihydroxybiphenyl 1,2-dioxygenase

CarC:

Carbapenem synthase

CAS:

Clavaminate synthase

DAOCS:

Deacetoxycephalosporin C synthase

DFT:

Density functional theory

DHBD:

Synonymous with BphC

DHBP:

2,3-Dihydroxybiphenyl

EXAFS:

Extended X-ray absorption fine structure

FIH-1:

Factor-inhibiting hypoxia-inducible factor-1

HGO:

Homogentisate 1,2-dioxygenase

HPCD:

Homoprotocatechuate 2,3-dioxygenase

HPPD:

4-Hydroxyphenylpyruvate dioxygenase

IPNS:

Isopenicillin N synthase

LigAB:

Synonymous with 4,5-PCD

MCD:

Magnetic circular dichroism

MndD:

MnII-dependent HPCD

MPC:

Metapyrocatechase (synonymous with 2,3-CTD)

NDO:

Naphthalene 1,2-dioxygenase

PCV:

Proclavaminate

PheOH:

Phenylalanine hydroxylase

TauD:

Taurine/α-KG dioxygenase

THA:

3-(2-Thienyl)-L-alanine

TrpOH:

Tryptophan hydroxylase

TyrOH:

Tyrosine hydroxylase

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Authors and Affiliations

  1. Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN, 55455, USA

    Kevin D. Koehntop, Joseph P. Emerson & Lawrence Que Jr

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  1. Kevin D. Koehntop
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  2. Joseph P. Emerson
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  3. Lawrence Que Jr
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Correspondence to Lawrence Que Jr.

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Koehntop, K.D., Emerson, J.P. & Que, L. The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen activation by mononuclear non-heme iron(II) enzymes. J Biol Inorg Chem 10, 87–93 (2005). https://doi.org/10.1007/s00775-005-0624-x

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