X-ray protein crystallography has been a new focus of our laboratory since the spring of 2011. We have solved over 50 non-redundant structures, including a couple of de novo protein structures and several reactive intermediate structures. Most of these structures are iron-based enzymes and a regulatory protein of signal transductions. Overall, structural characterization has become an integrated efforts in our biochemical, spectroscopic and structural studies of metallproteins/metalloenzymes and protein-based free radicals.


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)
(This paper was designated by teh 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).
Structures associated with this publication and released in the protein databank with the following PDB entries: 5KJ5, 5KLK, 5KLL, 5KLM, 5KLN, and 5KLO
Aldehyde dehydrogenases mediate the oxidation of highly reactive aldehyde compounds in the cell. This paper reveals a pitcher-and-catcher chemical mechanism of a hidden isomerization performed by a kynurenine pathway aldehyde dehydrogenase prior to the expected redox reaction. The figure above shows a critical catalytic intermediate caught in action by protein X-ray crystallography.



Capture of tetrahedral thiohemiacetal and thioacyl intermediates reveals an sp3-to-sp2 transition during an enzyme-mediated dehydrogenation
Huo L,^ Davis I,^ Liu F, Andi B, Esaki S, Hiroaki I, Li T, Hasegawa Y, Orville AM, and Liu A*
Nature Communications 2015, 6:5935 (DOI: 10.1038/ncomms6935).
Structures associated with this publication and released in the protein databank with following PDB entries: 4I25, 4I26, 4I1W, 4I2R, 4NPI, 4OE2, 4OU2, and 4OUB.
^: shared first authorship


Pirin is a non-heme iron-dependent redox regulator of NF-κB
Liu F, Rehmani I, Esaki S, Fu R, Chen L, Serroano V, and Liu A*
PNAS 2013, 110(24), 9722-9724 (DOI: 10.1073/pnas.1221743110).
Structures associated with this publication and released in the protein databank with the following PDB entries: 4GUL, 4EWA, 4EWE, 4ERO, 4EWD, and 4HLT.
(This paper reports our discovery of a novel non-heme iron protein-based redox sensor in cell nucleus for NF-κB signal transduction regulation).


The Power of two: arginine 51 and arginine 239* from a neighboring subunit are essential for catalysis in α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase
Huo L, Davis I, Chen L, and Liu A*
J. Biol. Chem. 288, 30862-30871 (DOI: 10.1074/jbc.M113.496869
Structures associated with this publication and released in the protein databank with the following PDB entries: 4IFK, 4IFO, 4IFR, and 4IG2.
In this work, we solved a catalytically active protein structure from a heterogeneous solution of simple mix of two dead mutant homodimers! In the resulting hybrid heterodimer one subunit contains a wild-type structure while in another subunit a double mutation is present. Such a catalytically active hybrid cannot be generated by molecular biology methods!.


Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling
Huo L,^ Liu F,^ Hiroaki I, Li T, Hasegawa Y, and Liu A*
PROTEINS 2014, 83(1), 178-187 (featured as a cover story by the journal).
Structures associated with this publication and released in the protein databank with the following PDB entries:: 4OFC, 4IH3, and 4IGN.
^: shared first authorship
This paper reports the crystal structure of catalytically active form of human ACMSD enzyme and the complex structure with bound ligand.


Evidence for a dual role of an active site histidine in α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase Huo L et al.
Biochemistry 51, 5811-5821.
Structures associated with this publication and released in the protein databank with the following PDB entries: 4ERA, 4ERG, 4ERI, and 4ERK
This paper reports a single mutation at the second ligand sphere (non-metal ligand) changes a decarboxylase's metal selectivity from zinc to iron.



Twenty other structures deposited and ready for publication in near future



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