B.S. Zhejiang Sci-Tech University
Ph.D. University of Texas at San Antonio
The Wang Lab studies oxygen activation and C–H/C–C bond functionalization by metalloenzymes.
Molecular oxygen is a powerful oxidant, but its reaction with ground-state singlet molecules is kinetically unfavorable due to its spin-forbidden nature. To harness the oxidizing power of oxygen and manipulate biomolecules, iron-containing enzymes are frequently employed by aerobic organisms. Heme and non-heme iron-dependent oxygenases represent two of the most ubiquitous and potent natural catalysts, while the contribution of the ligand sets to oxygen activation and reaction outcome remains largely unknown due to the massive variations between heme and non-heme systems. We aim to fill the knowledge gap through a comparative investigation of the biomedically essential oxygenases with specific ligand sets. Structural and spectroscopic techniques are used to probe the catalytic mechanisms and structure-function correlations of these systems.
Our research will broaden the understanding of iron-oxygen chemistry and establish the platform for therapeutic interventions.
15. Shin, I.; Wang, Y.; Liu, A. A new regime of the histidyl-ligated heme-dependent oxygenase superfamily. Proc. Natl. Acad. Sci. U. S. A. 2021, 118, in press (DOI: 10.1073/pnas.xxxxxxx (pending))
14. Wang, Y.; Shin, I.; Li, J.; Liu, A. Crystal structure of human cysteamine dioxygenase provides a structural rationale for its function as an oxygen sensor. J. Biol. Chem. 2021, 297, in press (DOI: 10.1016/j.jbc.2021.101176)
13. Wang, Y.; Davis, I.; Liu, A. Molecular rationale for partitioning between C-H and C-F bond activation in heme-dependent tyrosine hydroxylase. J. Am. Chem. Soc. 2021, 143(12), 4680-4693 (DOI: 10.1021/jacs.1c00175)
12. Shin, I.; Davis, I.; Nieves-Merced, K.; Wang, Y.; McHardy, S.; Liu A. A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by the spectroscopic and structural study. Chem. Sci. 2021, 12(11), 3984-3998 (DOI: 10.1039/D0SC06369J)
11. Wang, Y.*; Liu, KF.*; Yang, Y.; Davis, I.; Liu, A. Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens. Proc. Natl. Acad. Sci. U. S. A. 2020, 117(33), 19720-19730.(DOI: 10.1073/pnas.2005327117) (*Equal contribution)
10. Wang, Y.; Davis, I.; Yang, Y.; Davis, I.; Chen, Y.; Naik, S.; Griffith, W.; Liu A. Characterization of the non-heme iron center of cysteamine dioxygenase and its interaction with substrates. J. Biol. Chem. 2020, 295(33), 11789-11802. (DOI: 10.1074/jbc.RA120.013915)
9. Wang, Y.; Liu, A. Carbon-fluorine bond cleavage mediated by metalloenzymes. Chem. Soc. Rev. 2020, 49, 4906-4925. (DOI: 10.1039/C9CS00740G)
8. Nguyen, R.; Yang, Y.; Wang, Y.; Davis, I.; Liu, A. Substrate-assisted hydroxylation and O-demethylation in the peroxidase-like cytochrome P450 enzyme CYP121. ACS Catal. 2020, 10(2), 1628-1639. (DOI: 10.1021/acscatal.9b04596)
7. Wang, Y.; Davis, I.; Shin, I.; Wherritt, D.; Griffith, W.; Dornevil, K.; Colabroy, K.; Liu, A. Biocatalytic carbon-hydrogen and carbon-fluorine bond cleavage through hydroxylation promoted by a histidyl-ligated heme enzyme. ACS Catal. 2019, 9(6), 4764-4776. (DOI: 10.1021/acscatal.9b00231)
Featured by ACS Editors’ Choice and ACS LiveSlides
6. Wang, Y.; Shin, I.; Fu, Y.; Colabroy, K.; Liu, A. Crystal structures of L-DOPA dioxygenase from Streptomyces Sclerotialus. Biochemistry. 2019, 58(52), 5339-5350. DOI: 10.1021/acs.biochem.9b00396)
Invited original contribution for a special issue “Current Topics in Mechanistic Enzymology 2019”
5. Wang, Y.; Griffith, W.; Li, J.; Koto, T.; Wherritt, D.; Fritz, E.; Liu, A. Cofactor biogenesis in cysteamine dioxygenase: C-F bond cleavage with genetically incorporated unnatural tyrosine. Angew. Chem. Int. Ed. 2018, 57(27), 8149-8153. (DOI: 10.1002/ange.201803907)
4. Li, J.; Griffith, W.; Davis, I.; Shin, I.; Wang, J.; Li, F.; Wang, Y.; Wherritt, D.; Liu, A. Cleavage of a carbon–fluorine bond by an engineered cysteine dioxygenase. Nat. Chem. Biol. 2018, 14(9), 853-860. (DOI: 10.1038/s41589-018-0085-5)
3. Wang, Y.; Li, J.; Liu, A. Oxygen activation by mononuclear nonheme iron dioxygenases involved in the degradation of aromatics. J. Biol. Inorg. Chem. 2017, 22(2), 395-405. (DOI: 10.1007/s00775-017-1436-5) Invited article for a special issue “60 Years of Oxygen Activation”
2. Yang, Y.; Davis, I.; Ha, U.; Wang, Y.; Shin, I.; Liu, A. A pitcher-and-catcher mechanism drives endogenous substrate isomerization by a dehydrogenase in kynurenine metabolism. J. Biol. Chem. 2016, 291(51), 26252-26261. (DOI: 10.1074/jbc.M116.759712)
Featured as "Papers of the Week”
1. Zuo, B.; Liu, Y.; Wang, L.; Zhu, Y.; Wang, Y.; Wang, X. Depth profile of the segmental dynamics at a poly(methyl methacrylate) film surface. Soft Matter, 2013,9, 9376-9384. (DOI: 10.1039/C3SM51658J)
The Wang Lab is recruiting! Students and postdocs interested in protein chemistry are welcome to join us. Please send a CV to Dr. Wang.