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The Metalloprotein Research Laboratory in San Antonio 


Principal Investigator: Aimin (Feradical) Liu, Ph.D., FRSC, Professor and Lutcher Brown Distinguished Chair in Biochemistry  

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RESEARCH INTEREST

 

Research in our lab investigates how biomolecules utilize metals to perform the chemistry necessary for life. Our ongoing research projects lie at the nexus of chemistry and biology and span a broad range of topics, including mechanistic enzymology, chemical biology, bioinorganic chemistry, and biophysics. Specifically, we study amino acid metabolism, the mechanisms of oxygen activation by metalloproteins, C-H/C-F bond functionalization, natural product biosynthesis, protein cofactor biogenesis, free radical enzymology, and metalloproteins-mediated signal transduction and gene regulation. To explore these phenomena, we utilize a wide array of chemical and biophysical techniques, such as EPR/ENDOR and NMR spectroscopies, LC-MS spectrometry, Isothermal titration calorimetry, stopped-flow and rapid freeze-quench kinetics, protein X-ray crystallography, and genetic code expansion strategies for specific unnatural amino acid incorporation into proteins.

 

Ongoing research projects
 »    Mechanistic enzymology of tryptophan-kynurenine pathway and its relation to neuropsychiatry and cancer immunotherapy
 »    Cofactor biogenesis in iron and copper proteins to endow new functions or maximize the catalytic power
 »    Heme-dependent chemistry in tyrosine oxidations for anticancer and antimicrobial drug development
 »    Metalloprotein-mediated redox sensing in response to oxidative stress
 

ACCOLADE (selected)

 

1991     Presidential Award for Scholar Excellence of Graduate Research, Chinese Academy of Sciences (CAS), China

1996     Royal Society - K.C. Wong Fellowship, the Royal Society, U.K.

2002     Paul D. Boyer Award for Research Excellence, University of Minnesota, MN

2003     Ralph E. Powe Junior Faculty Enhancement Award in Life Sciences, The Oak Ridge Associated Universities (ORAU)

2008     Visiting Professorship at Kansai University, Osaka, Japan

2009     Georgia Research Alliance (GCC) Distinguished Cancer Scholar, State of Georgia

2014     Outstanding Senior Faculty Award, College of Arts and Sciences, Georgia State University

2015     Distinguished University Professor, Georgia State University (relinquished in 01/2016 due to relocation to UTSA)

2016     Lutcher Brown Distinguished Chair in Biochemistry, The University of Texas at San Antonio

2021     Fellow of the Royal Society of Chemistry (FRSC)

2021     Inducted into The UTSA Academy of Distinguished Researchers

 

REPRESENTATIVE PUBLICATIONS (recent five years only)

 

✓    Molecular rationale for partitioning between C-H and C-F bond activation in heme-dependent tyrosine hydroxylase
Wang Y, Davis I, Shin I, Xu H, and Liu A*
JACS, 2021, 143(12), 4680-4693 [DOI]: 10.1021/jacs.1c00175   [PDF]

✓    A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by de novo crystal structural and spectroscopic study
Shin I, Davis I, Nieves-Merced K, Wang Y, McHardy S, and Liu A*
Chem. Sci., 2021, 12(11), 3984-3998 [DOI]: 10.1039/D0SC06369J   [PDF]

✓    Formation of monofluorinated radical cofactor in galactose oxidase through copper-mediated C−F bond scission
Li J, Davis I, Griffith WP, and Liu A*
JACS, 2020, 142(44), 18758-18757 [DOI]: 10.1021/jacs.0c08992   [PDF]

✓    Observing 3-hydroxyanthranilate-3,4-dioxygenase in action through a crystalline lens
Wang Y, Liu KF, Yang Y, Davis I, and Liu A*
PNAS, 2020, 117(33), 19720-19730  (PNAS Direct Submission) [DOI]: 10.1073/pnas.2005327117   [PDF]

✓    Characterization of the non-heme iron center of cysteamine dioxygenase and its interaction with substrates
Wang Y, Davis I, Yang Y, Chen Y, Naik SG, Griffith WP, and Liu A*
JBC, 2020, 295(33), 11789-11802   [DOI]: (10.1074/jbc.RA120.013915)   [PDF]

✓    Substrate-assisted hydroxylation and O-demethylation in the peroxidase-like cytochrome P450 enzyme CYP121
Nguyen RC, Yang Y, Wang Y, Davis I, and Liu A*
ACS Catalysis, 2020, 10(2), 1628-1639   [DOI]: 10.1021/acscatal.9b04596   [PDF]   [LiveSlides]

✓    Quaternary structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase (ACMSD) controls its activity
Yang Y, Davis I, Matsui T, Rubalcava I, and Liu A*
JBC, 2019, 294(30), 11609-11621   [DOI]: 10.1074/jbc.RA119.009035   [PDF]   featured as JBC cover story    

✓    Biocatalytic carbon-hydrogen and carbon-fluorine bond cleavage through hydroxylation promoted by a histidyl-ligated heme enzyme
Wang Y, Davis I, Shin I, Wherritt DJ, Griffith WP, Dornevil K, Colabroy KL, and Liu A*
ACS Catalysis, 2019, 9(6), 4764-4776   [DOI]: 10.1021/acscatal.9b00231   [PDF]   [LiveSlides]
  featured by ACS Editors’ Choice

✓    Probing the Cys-Tyr cofactor biogenesis in cysteine dioxygenase by the genetic incorporation of fluorotyrosine
Li J, Koto T, Davis I, and Liu A*
Biochemistry, 2019, 58(17), 2218-2227   [DOI]: 10.1021/acs.biochem.9b00006   [PDF]

✓    Cleavage of a carbon–fluorine bond by an engineered cysteine dioxygenase
Li J, Griffith WP, Davis I, Shin I, Wang J, Li F, Wang Y, Wherritt D, and Liu A*
Nat. Chem. Biol., 2018, 14(9), 853-860   [DOI]: 10.1038/s41589-018-0085-5   [PDF]

✓    Adapting to oxygen: 3-Hydroxyanthrinilate 3,4-dioxygenase employs loop dynamics to accommodate two substrates with disparate polarities
Yang Y, Liu F*, and Liu A*
JBC, 2018, 293(27), 10415-10424   [DOI]:
10.1074/jbc.RA118.002698    [PDF]   featured as JBC cover story     

✓    Cofactor biogenesis in cysteamine dioxygenase: C-F bond cleavage with genetically incorporated unnatural tyrosine
Wang Y, Griffith WP, Li J, Koto, T, Wherritt D, Fritz E, and Liu A*
Angew. Chem. Int. Ed., 2018, 57(27), 8149-8153   [DOI]: 10.1002/ange.201803907  
 [PDF]

✓    Reassignment of the human aldehyde dehydrogenase ALDH8A1 (ALDH12) to the kynurenine pathway in tryptophan catabolism
Davis I, Yang Y, Wherritt D, and Liu A*
JBC, 2018, 293(25), 9594-9603   [DOI]: (10.1074/jbc.RA118.003320)   [PDF]

✓    Stepwise O-atom transfer in heme-based tryptophan dioxygenase: Role of substrate ammonium in epoxide ring opening
Shin I, Ambler BR, Wherritt DJ, Griffith WP, Maldonado AC, Altman RA, and Liu A*
JACS, 2018, 140(12), 4372-4379   [DOI]: 10.1021/jacs.8b00262   [PDF]

✓    High-frequency/high-field EPR and theoretical studies of tryptophan-based radicals
Davis I, Koto T, Terrell JR, Kozhanov A, Krzystek J, and Liu A*
JPC, 2018, 122(12), 3170-3176   [DOI]: 10.1021/acs.jpca.7b12434   [PDF]

✓    Probing ligand exchange in the P450 enzyme CYP121 from Mycobacterium tuberculosis: Dynamic equilibrium of the distal heme ligand
Fielding AJ, Dornevil K, Ma L, Davis I, and Liu A*
JACS, 2017, 139(48), 17484-17499   [DOI]: 10.1021/jacs.7b08911   [PDF]

✓    Crosslinking of dicyclotyrosine by cytochrome P450 CYP121 from Mycobacterium tuberculosis proceeds through a catalytic shunt pathway
Dornevil K, Davis I, Fielding AJ, Terrell JR, Ma L, and Liu A*
JBC, 2017, 292(33), 13645-13657   [DOI]: 10.1074/jbc.M117.794099   [PDF]

✓    Hypertryptophanemia due to tryptophan 2,3-dioxygenase deficiency
Ferreira F*, Shin I, Sosova I, Dornevil K, Jain Shailly, Dewey D, Liu F, and Liu A*
Mol. Genet. Metab., 2017, 120(4), 317-324   [DOI]: 10.1016/j.ymgme.2017.02.009   [PDF]

✓    A pitcher-and-catcher mechanism drives endogenous substrate isomerization by a dehydrogenase in kynurenine metabolism
Yang Y, Davis I, Ha U, Wang Y, Shin I, and Liu A*
JBC, 2016, 291(51), 26252-26261   [DOI]: 10.1074/jbc.M116.759712    [PDF]

(featured as a "Papers of the Week" and selected, after publication, in a collection of representative papers in an enzymology virtual issue)

 

OUTREACH & SERVICE

 

Federal grant review panelist

 ‣    Charter Member, The Macromolecular Structure and Function A (MSFA) Study Section, NIH Center for Scientific Review, 7/2019-6/2023

 ‣    Panelist, NIH Center for Scientific Review Special Emphasis Panel for Continuous Submission and Conflict Review, 2017/03 ZRG1 BCMB-H 02 M

 ‣    Panelist, NIH Center for Scientific Review Special Emphasis Panel, Biochemistry and Biophysical Chemistry, 2016/03 ZRG1 F04B-D (20)

 ‣    Panelist, NIH Center for Scientific Review Special Emphasis Panel, Biochemistry and Biophysical Chemistry, 2014/10 ZRG1 F04B-D (20) L

 ‣    Panelist, NSF CAREER Award Review Panels: 2012 (CLP-MCB joint panel), 2017 (CLP), and 2018 (CLP)

 ‣    Panelist, NSF proposal review panels, 2009 (MCB), 2015 (MCB), 2019 (CLP), and 2021 (CLP)

 ‣    Panelist, The Macromolecular Structure and Function A (MSFA) Study Section, NIH Center for Scientific Review, 2006

 ‣    External reviewer for ACS PRF, Biotechnology and Biological Sciences Research Council (BBSRC) of UK, Medical Research Council (MRC) of UK,  ‣    Le financement sur projet au service de la Recherche (ANR, French National Research Agency), and Einstein Stiftung Berlin of Germany.

 

Elected role in professional organization

 

2010-2  Elected member, EMR User Committee, The National High Magnetic Field Laboratory

2013     Elected member, College promotion & tenure committee – the natural and computational sciences (elected at large seat)

2014-6  Faculty senator, Georgia State University Senate

2015     Elected member, Triennial evaluation committee of College of Arts & Sciences Dean

2015-7  Alternate councilor, American Chemical Society (ACS) Division of Biological Chemistry

 

Scientific conference/meeting

 

2010     Session chair, The Inaugural Annual Southeast Enzyme Conference

2011     Chair, 40th Southeastern Magnetic Resonance Conference (SEMRC 2011)

2012     Discussion leader, Gordon Research Conference - Protein Cofactors, Radicals & Quinones, South Hadley, MA

2014-5  Program Committee Member, Enzymes in Drug Discovery

2016     Discussion leader, Gordon Research Conference - Metals in Biology, Ventura, CA

2017     Symposium Chair: Metalloprotein-initiated signaling transduction response to redox stress, The 253rd ACS National Meeting, San Francisco

2017     Discussion Leader, Gordon Research Conference – Enzymes, Coenzymes, Metabolic Pathways, Waterville Valley, NH

2019     Session Chair, 26th Enzyme Mechanisms Conference, New Orleans, LA

 

MAJOR SOURCE OF FUNDING

 

Current major research grants: NIH/NIGMS R01GM108988 and NSF CHE-1808637