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The Metalloprotein Research Laboratory 


Dr. Aimin Liu (a.k.a.: Feradical), Professor and Lutcher Brown Distinguished Chair in Biochemistry  

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RESEARCH INTEREST

 

Research in our lab studies how biomolecules utilize metals to perform the chemistry necessary for life. Specifically, we study the mechanisms of oxygen activation by metalloenzymes and metalloproteins-mediated signal transduction regulation. To explore these phenomena, we utilize a wide array of chemical and biophysical techniques, such as EPR/ENDOR spectroscopy, stopped-flow rapid kinetics, and protein X-ray crystallography. Our on-going research projects lie at the nexus of chemistry and biology and span a broad range of topics including mechanistic enzymology, cofactor biogenesis, radical enzymology, natural product biosynthesis, metalloprotein-mediated redox stress-linked transcriptional activation and gene regulation mechanisms.

 

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 to prevent oxidative stress
 

SELECTED REPRESENTATIVE PUBLICATION (recent five years only)

 

✓    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*
J. Biol. Chem., 2018, 293(27), 10415-10424   [DOI]:
10.1074/jbc.RA118.002698    [PDF]   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*
J. Biol. Chem., 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*
J. Am. Chem. Chem., 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*
J. Phys. Chem. A, 2018, 122(12), 3170-3176   [DOI]: 10.1021/acs.jpca.7b12434   [PDF]

✓    Radical trapping study of the relaxation of bis-Fe(IV) MauG
Davis I, Koto T, and Liu A*
Reactive Oxygen Species, 2018, 5(13), 46-55   [DOI]: 10.20455/ros.2018.801   [PDF]

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

✓    Crosslinking of dicyclotyrosine by the cytochrome P450 enzyme CYP121 from Mycobacterium tuberculosis proceeds through a catalytic shunt pathway
Dornevil K, Davis I, Fielding AJ, Terrell JR, Ma L, and Liu A*
J. Biol. Chem., 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*
J. Biol. Chem., 2016, 291(51), 26252-26261   [DOI]: 10.1074/jbc.M116.759712    [PDF]

(designated by the editors as a "Papers of the Week" and selected, after publication, in a collection of a representative snapshot of recent papers in the field of enzymology in a virtual issue)

✓    An iron reservoir to the catalytic metal: The rubredoxin iron in an extradiol dioxygenase
Liu F, Geng J, Gumpper RH, Barman A, Davis I, Ozarowski A, Hamelberg D, and Liu A*
J. Biol. Chem., 2015, 290(25), 15621-15634   [DOI]: 10.1074/jbc.M115.650259    [PDF]

✓    Probing bis-Fe(IV) MauG: Experimental evidence for the long-range charge-resonance model
Geng J, Davis I, and Liu A*
Angew. Chem. Int. Ed., 2015, 54, 3692-3696   [DOI]: 10.1002/anie.201410247    [PDF]

✓    Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action
Huo L, Davis I, Liu F, Andi B, Esaki S, Hiroaki I, Li T, Hasegawa Y, Orville AM, and Liu A*
Nat. Commun., 2015, 6:5935   [DOI]: 10.1038/ncomms6935  [PDF]

✓    Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling
Huo L, Liu F, Hiroaki I, Hasegawa Y, and Liu A*
PROTEINS, 2014, 83(1), 178-187   [DOI]: 10.1002/prot.24722  [PDF]

✓    Pirin is an iron-dependent redox regulator of NF-κB     (F1000Prime Recommended Article)
Liu F, Rehmani I, Esaki S, Fu R, Chen L, Serroano V, and Liu A*
Proc. Natl. Acad. Sci. USA, 2013, 110(24), 9722-9727 (PNAS Direct Submission)   [DOI]: 10.1073/pnas.1221743110  [PDF]

✓    Tryptophan-mediated charge-resonance stabilization in the bis-Fe(IV) redox state of MauG
Geng
J, Dornevil K, Davidson VL, and Liu A*
Proc. Natl. Acad. Sci. USA, 2013, 110(24), 9639-9644 (PNAS Direct Submission)   [DOI]: 10.1073/pnas.1301544110   [PDF]

✓    Diradical intermediate within the context of tryptophan tryptophylquinone biosynthesis     ( F1000Prime Recommended Article)
Yukl
ET, Liu F, Krzystek J, Shin S, Jensen LMR, Davidson VL, Wilmot CM, and Liu A*
Proc. Natl. Acad. Sci. USA, 2013, 110(12), 4569-4573 (PNAS Direct Submission)   [DOI]: 10.1073/pnas.1215011110   [PDF]

✓    The power of two: arginine 51 and arginine 239* from a neighboring subunit are essential for catalysis in ACMS decarboxylase
Huo
L, Davis I, Chen L, and Liu A*
J. Biol. Chem., 2013, 288(43), 30862-30871   [DOI]: 10.1074/jbc.M113.496869   [PDF]

 

ACCOLADE (selected)

 

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 Distinguished Cancer Scholar

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

2015-6  Distinguished University Professorship, Georgia State University (voluntarily relinquished in 01/2016 due to relocation to UTSA

2016-    Endowed Professorship: Lutcher Brown Distinguished Chair in Biochemistry, The University of Texas at San Antonio

 

OUTREACH & SERVICE

 

Grant reviewer

 ‣    National Institutes of Health (NIH) proposal review panelist: 2006, 2014, 2016, and 2017

 ‣    National Science Foundation (NSF) proposal review panelist: 2009, 2012, 2015, 2017, and 2018

 ‣    Ad hoc proposal reviewer for the Biotechnology and Biological Sciences Research Council (BBSRC), UK, since 2010

 ‣    Ad hoc proposal reviewer for the Medical Research Council (MRC), UK, since 2013

 

Editorial appointment

 

2013-present   Editorial board member, BBA Proteins and Proteomics

2014-8            Editorial advisory board member, Journal of Biological Inorganic Chemistry (JBIC)

2016-present   Editorial board member, Reactive Oxygen Species (ROS)

2017-present   Editorial Board Member, Frontiers in Bioscience

2017-present   Editorial Board Member, Journal of Biochemistry and Chemical Sciences

 

Elected role in professional organization

 

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

2013-    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 deano

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

2012     Discussion leader, GRC - Protein Cofactors, Radicals & Quinones, South Hadley, MA

2014-5  Program Committee Member, Enzymes in Drug Discovery

2015     Discussion leder, GRC - Metals in Biology, Ventura, CA

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

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

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

 

MAJOR SOURCE OF FUNDING

 

NIGMS/NIH; NIMH/NIH; and NSF