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Research Interests: Enzymology & Metallobiochemistry
My research program lies at the interface of biochemistry, bioinorganic chemistry, spectroscopy, and cellular biology. The current ongoing research is directed towards understanding the interaction of metal ions in enzymes/proteins with other chemical and biological molecules. My long term goal is to determine the chemical basis for the biological roles and physiological effects of metal ions. At present, my laboratory has three concurrent research foci. The first project concerns the molecular mechanism of signal transduction regulation. My laboratory employs a wide array of chemical, biochemical, bioinformatics, molecular and cellular biology, and spectroscopic methods to study the structure-function relationships of pirin, a newly identified nuclear metalloprotein that participates in cell signaling through modulation of NF-κB, an inducible transcription factor. Our second project concerns tryptophan metabolism and neuropsychiatric problems. We are engaged in studying mechanistic enzymology and regulation of tryptophan’s kynurenine pathway. We are currently elucidating the chemical mechanism of an important decarboxylase of the kynurenine pathway that catalyzes a novel metal-dependent oxidant-independent decarboxylation reaction. Our third project is placed on radical enzymology, which studies oxygen activation, reactive iron intermediates and protein-based substrate radicals in the enzymes that perform tryptophan oxidation.

Recent Publications (01/2003-07/2008)
Wang Y., Graichen ME, Liu A, Pearson AR, Wilmot CM, and Davidson VL (2003) MauG, a novel di-heme protein required for tryptophan tryptophylquinone biogenesis. Biochemistry, 42(24), 7318–7325. [Abstract]
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Ryle MJ, Liu A, Muthukumaran RB, Koehntop KD, McCracken J, Que L Jr., and Hausinger RP (2003) O2- and α-ketoglutarate-dependent tyrosyl radical formation in TauD, an α-keto acid-dependent non-heme iron dioxygenase. Biochemistry, 42(7), 1854–1862.
[Abstract]
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Jones LH, Liu A, Davidson VL (2003) An engineered CuA amicyanin capable of intramolecular electron transfer reactions. J. Biol. Chem., 278(47), 47269–47274. [Abstract]
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Liu P, Liu A, Yan F, Wolfe MD, Lipscomb JD, and Liu HW (2003) Biochemical and spectroscopic studies on (S)-2-hydroxypropylphosphonic acid epoxidase: a novel mononuclear non-heme iron enzyme. Biochemistry, 42(40), 11577–11586. [Abstract]
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Ryle MJ, Koehntop KD, Liu A, Que L Jr, and Hausinger RP (2003) Interconversion of two oxidized forms of taurine/α-ketoglutarate dioxygenase, a nonheme iron hydroxylase: Evidence for bicarbonate binding. Proc. Natl. Acad. Sci. U.S.A., 100(7), 3790–3795.
[Abstract]
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Zhou T, Mo Y, Liu A, and Tsai KR (2004) Enzymatic mechanism of Fe-only hydrogenase: density functional study on H-H making/breaking at the diiron cluster with concerted proton and electron transfers. Inorg. Chem., 43(3), 923–930.
[Abstract]
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Li T, Walker AL, Iwaki H, Hasegawa Y, Liu A (2005) Kinetic and spectroscopic characterization of ACMSD from Pseudomonas fluorescens reveals a pentacoordinate mononuclear metallocofactor. J. Am. Chem. Soc., 127(35), 12282–12290.
[Abstract]
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Colabroy KL, Zhai H, Li T, Ge Y, Zhang Y, Liu A, Ealick SE, McLafferty FW, and Begley TP (2005) The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate. Biochemistry, 44(21), 7623–7631. [Abstract]
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Yan F, Li T, Lipscomb JD, Liu A, and Liu H-w (2005) Site-directed mutagenesis and spectroscopic studies of the iron-binding site of (S)-2-hydroxypropylphosphonic acid epoxidase. Arch. Biochem. Biophys., 442(1), 82–91.
[Abstract]
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Li T, Iwaki H, Fu R, Hasegawa Y, Zhang H, Liu A (2006) α-Amino-β-carboxymuconic-ε-semialdehyde decarboxylase (ACMSD) is a new member of the amidohydrolase superfamily. Biochemistry, 45(21), 6628–6634.
[Abstract]
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Martynowski D, Eyobo Y, Li T, Yang K, Liu A, and Zhang H(2006) Crystallographic analysis of α-Amino-β-carboxymuconic-ε-semialdehyde decarboxylase (ACMSD): Insight into the active site and catalytic mechanism of a novel decarboxylation reaction. Biochemistry, 45(35), 10412–10421. [Abstract] [PDF]
Liu A and Zhang H (2006) Transition metal-catalyzed nonoxidative decarboxylation reactions. Biochemistry, 45(35),10407–10411.
(This paper is listed as a 2006 Hot Article on the ACS publications web site.)
[Abstract]
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Li T, Ma J, Hosler JP, Davidson VL and Liu A (2007) Detection of transient intermediates in the metal-dependent non-oxidative decarboxylation catalyzed by α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase. J. Am. Chem. Soc. (Comm.), 129(30), 9278–9279.
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Yan F, Moon S-J, Liu P, Zhao Z, Lipscomb JD, Liu A, and Liu H-w (2007) Determination of the substrate binding mode to the active site iron of (S)-2-hydroxypropylphosphonic acid epoxidase using 17O-enriched substrates and substrate analogues. Biochemistry, 46(44), 12628–12638.
[Abstract] [PDF]
Liu A, Li T, and Fu R (2007) Amidohydrolase Superfamily. In: Encyclopedia of Life Sciences. John Wiley & Sons, Ltd: Chichester http://www.els.net/ [DOI: 10.1002/9780470015902.a0020546] (an invited review article).
[Abstract] [PDF]
Li X, Fu R, Liu A, and Davidson VL (2008) Kinetic and physical evidence that the di-heme enzyme MauG tightly binds to a biosynthetic precursor of methylamine dehydrogenase with incompletely formed tryptophan tryptophylquinone. Biochemistry, 47(9), 2908–2912. [Abstract] [PDF]
Munos JW, Moon S-J, Mansoorabadi SO, Hong L, Yan F, Liu A, and Liu H-w (2008) Purification and characterization of the epoxidase catalyzing the formation of fosfomycin from Pseudomonas syringae. Biochemistry, 47, in press.
Li X, Fu R, Lee S, Krebs C, Davidson VL, and Liu A (2008) A catalytic di-heme bis-Fe(IV) form of MauG, Alternative to an Fe(IV)=O porphyrin radical. Proc. Natl. Acad. Sci. U.S.A., 105(25), 8597–8600. [Abstract] [PDF]
Liu A (2008) EPR in Enzymology. Wiley Encyclopedia of Chemical Biology, John Wiley & Sons, Inc. (invited article). [Abstract]
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