The Metalloprotein Research Laboratory in San Antonio
Principal Investigator: Aimin Liu (Feradical), Ph.D., Professor of Chemistry & Lutcher Brown Distinguished Chair in Biochemistry
RESEARCH INTEREST: Amino Acid Oxidation and Metabolism
Research in our lab @UTSA 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, NMR, and resonance Raman 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.
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RESEARCH PROJECTS & PRESENT FUNDING
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
Active extramural funding
‣ NIH R01GM108988, PI, 08/01/2022 - 08/31/2026
SCHOLARLY ACTIVITIES - RESEARCH FINDINGS (since 01/2016 @ UTSA)
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We discovered a novel catalytic heme cofactor with a single thioether bond and a new heme-binding motif.
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We obtained a high-resolution ferric-hydroperoxo intermediate crystal structure. This is a long-awaited intermediate structure in the heme chemistry field obtained directly in a heme enzyme during catalysis with a substrate.
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We discovered the missing human gene for a dehydrogenase in the primary tryptophan catabolic pathway, which was erroneously assigned (by others) to 9-cis-retinal dehydrogenase previously.
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We discovered a genetic disorder, hypertryptophanemia, through collaboration with a medical geneticist and revealed its biochemistry origin.
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We described a competing catalytic C–H/C–F bond activation by a single iron center and discovered a new C-F bond cleavage mechanism.
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We brought the genetic code expansion technology to study protein-derived cofactors with site-specific substitution of unnatural amino acids.
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We identified a novel heme cofactor in a hydroxylase (oxygenases) and determined its crystal structure, spectroscopic properties, and reactivities.
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We defined a new histidyl-ligated heme-dependent aromatic oxygenase (HDAO) superfamily.
RECENT REPRESENTATIVE PUBLICATIONS (since 2016 @ UTSA)
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Charge maintenance during catalysis in non-heme iron oxygenases
Traore ES and Liu A*
ACS Catalysis, 2022, 12(10), 6191-6208
[DOI]:
10.1021/acscatal.1c04770
[PDF]
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A new regime of heme-dependent aromatic oxygenase superfamily
Shin I, Wang Y, and Liu A*
PNAS, 2021, 118(43), e210656
[DOI]:
10.1073/pnas.2106561118
[PDF]
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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]
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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]
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Crystal structure of human cysteamine dioxygenase provides a structural rationale for its function as an oxygen sensor
Wang Y, Shin I, Li J, and Liu A*
JBC, 2021, 297(4), 101176 (1-10)
[DOI]: (10.1074/jbc.RA120.013915)
[PDF]
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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]
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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]
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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]
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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]
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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]
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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)
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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]
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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]
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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]
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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]
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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]
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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]
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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]
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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]
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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]
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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]
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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 a virtual issue of Enzymology)
ACCOLADE (selected)
1991
Presidential Award for Scholar Excellence of Graduate Research, Chinese Academy of Sciences (CAS), China
1996
Royal Society - K.C. Wong Fellow, The Royal Society, London, UK
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 on 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
Elected into The UTSA Academy of Distinguished Researchers (ADR)
2021
Elected 2021 AAAS Fellows
2022
National Science Foundation (NSF) Accomplishment-Based Renewal (ABR) award
OUTREACH & SERVICE
Grant review
‣ Charter Member, The Macromolecular Structure and Function A (MSFA) Study Section, NIH Center for Scientific Review, 7/2019-6/2023Elected 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 lead, Gordon Research Conference - Protein Cofactors, Radicals & Quinones, South Hadley, MA
2014-5
Program Committee Member, Enzymes in Drug Discovery
2016
Discussion lead, 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 Lead, Gordon Research Conference – Enzymes, Coenzymes, Metabolic Pathways, Waterville Valley, NH
2019
Session Chair, 26th Enzyme Mechanisms Conference (EMC2019), New Orleans, LA
2022
Discussion lead, Gordon Research Conference - Chemistry and Biology of Tetrapyrroles, Newport, RI
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