Geometric and electronic structures of the His-Fe(IV)=O and His-Fe(IV)-Tyr hemes of MauG.
Biosynthesis of the tryptophan tryptophylquinone (TTQ) cofactor activates the enzyme methylamine dehydrogenase. The diheme enzyme MauG catalyzes O-atom insertion and cross-linking of two Trp residues to complete TTQ synthesis. Solution optical and Mössbauer spectroscopic studies have indicated that the reactive form of MauG during turnover is an unusual bisFe(IV) intermediate, which has been formulated as a His-ligated ferryl heme [Fe(IV)=O] (heme A), and an Fe(IV) heme with an atypical His/Tyr ligation (heme B). In this study, Fe K-edge X-ray absorption spectroscopy and extended X-ray absorption fine structure studies have been combined with density functional theory (DFT) and time-dependent DFT methods to solve the geometric and electronic structures of each heme site in the MauG bisFe(IV) redox state. The ferryl heme site (heme A) is compared with the well-characterized compound I intermediate of cytochrome c peroxidase. Heme B is unprecedented in biology, and is shown to have a six-coordinate, S = 1 environment, with a short (1.85-Å) Fe-O(Tyr) bond. Experimentally calibrated DFT calculations are used to reveal a strong covalent interaction between the Fe and the O(Tyr) ligand of heme B in the high-valence form. A large change in the Fe-O(Tyr) bond distance on going from Fe(II) (2.02 Å) to Fe(III) (1.89 Å) to Fe(IV) (1.85 Å) signifies increasing localization of spin density on the tyrosinate ligand upon sequential oxidation of heme B to Fe(IV). As such, O(Tyr) plays an active role in attaining and stabilizing the MauG bisFe(IV) redox state.
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Lyndal M R
LM
Jensen
Yergalem T
YT
Meharenna
Victor L
VL
Davidson
Thomas L
TL
Poulos
Britt
B
Hedman
Carrie M
CM
Wilmot
Ritimukta
R
Sarangi
D015502:Absorptiometry, Photon; D003432:Cross-Linking Reagents / Q000737:chemistry; D004583:Electrons; D006418:Heme / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011789:Quantum Theory; D014443:Tyrosine / Q000737:chemistry*
D003432:Cross-Linking Reagents; D014443:Tyrosine; D006418:Heme; D006639:Histidine; D007501:Iron; C021567:methylamine dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010100:Oxygen