PDBsum entry 4fb1

Oxidoreductase/electron transfer

PDB id: 4fb1

Contents

Protein chains

354 a.a.

125 a.a.

376 a.a.

Ligands

HEC ×4

MES ×2

Metals

_NA ×3

_CA ×2

Waters ×656

References listed in PDB file

Key reference

• Title: Diradical intermediate within the context of tryptophan tryptophylquinone biosynthesis.
• Authors: E.T.Yukl, F.Liu, J.Krzystek, S.Shin, L.M.Jensen, V.L.Davidson, C.M.Wilmot, A.Liu.
• Ref.: Proc Natl Acad Sci U S A, 2013, 110, 4569-4573. [DOI no: 10.1073/pnas.1215011110]
• PubMed id: 23487750

Abstract

Despite the importance of tryptophan (Trp) radicals in biology, very few radicals have been trapped and characterized in a physiologically meaningful context. Here we demonstrate that the diheme enzyme MauG uses Trp radical chemistry to catalyze formation of a Trp-derived tryptophan tryptophylquinone cofactor on its substrate protein, premethylamine dehydrogenase. The unusual six-electron oxidation that results in tryptophan tryptophylquinone formation occurs in three discrete two-electron catalytic steps. Here the exact order of these oxidation steps in the processive six-electron biosynthetic reaction is determined, and reaction intermediates are structurally characterized. The intermediates observed in crystal structures are also verified in solution using mass spectrometry. Furthermore, an unprecedented Trp-derived diradical species on premethylamine dehydrogenase, which is an intermediate in the first two-electron step, is characterized using high-frequency and -field electron paramagnetic resonance spectroscopy and UV-visible absorbance spectroscopy. This work defines a unique mechanism for radical-mediated catalysis of a protein substrate, and has broad implications in the areas of applied biocatalysis and understanding of oxidative protein modification during oxidative stress.