Aimin Liu

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Name: Liu, Aimin

Organization: Georgia State University , USA

Department: Department of Chemistry & Center for Diagnostics and Therapeutics

Title: Professor(PhD)

TOPICS

Organic Chemistry

Chemicals
References

Probing Bis-FeIV MauG: Experimental Evidence for the Long-Range Charge-Resonance Model

Co-reporter:Dr. Jiafeng Geng;Ian Davis ;Dr. Aimin Liu

Angewandte Chemie International Edition 2015 Volume 54( Issue 12) pp:3692-3696

Publication Date(Web):

DOI:10.1002/anie.201410247

Abstract

The biosynthesis of tryptophan tryptophylquinone, a protein-derived cofactor, involves a long-range reaction mediated by a bis-Fe^IV intermediate of a diheme enzyme, MauG. Recently, a unique charge-resonance (CR) phenomenon was discovered in this intermediate, and a biological, long-distance CR model was proposed. This model suggests that the chemical nature of the bis-Fe^IV species is not as simple as it appears; rather, it is composed of a collection of resonance structures in a dynamic equilibrium. Here, we experimentally evaluated the proposed CR model by introducing small molecules to, and measuring the temperature dependence of, bis-Fe^IV MauG. Spectroscopic evidence was presented to demonstrate that the selected compounds increase the decay rate of the bis-Fe^IV species by disrupting the equilibrium of the resonance structures that constitutes the proposed CR model. The results support this new CR model and bring a fresh concept to the classical CR theory.

Probing Bis-FeIV MauG: Experimental Evidence for the Long-Range Charge-Resonance Model

Co-reporter:Dr. Jiafeng Geng;Ian Davis ;Dr. Aimin Liu

Angewandte Chemie 2015 Volume 127( Issue 12) pp:3763-3767

Publication Date(Web):

DOI:10.1002/ange.201410247

Abstract

Bis-Fe(IV): nature’s sniper for long-range oxidation

Co-reporter:Jiafeng Geng;Ian Davis;Fange Liu

JBIC Journal of Biological Inorganic Chemistry 2014 Volume 19( Issue 7) pp:1057-1067

Publication Date(Web):2014 October

DOI:10.1007/s00775-014-1123-8

Iron-dependent enzymes are prevalent in nature and participate in a wide range of biological redox activities. Frequently, high-valence iron intermediates are involved in the catalytic events of iron-dependent enzymes, especially when the activation of peroxide or molecular oxygen is involved. Building on the fundamental framework of iron–oxygen chemistry, these reactive intermediates constantly attract significant attention from the enzymology community. During the past few decades, tremendous efforts from a number of laboratories have been dedicated to the capture and characterization of these intermediates to improve mechanistic understandings. In 2008, an unprecedented bis-Fe(IV) intermediate was reported in a c-type diheme enzyme, MauG, which is involved in the maturation of a tryptophan tryptophylquinone cofactor of methylamine dehydrogenase. This intermediate, although chemically equivalent to well-characterized high-valence iron intermediates, such as compound I, compound ES, and intermediate Q in methane monooxygenase, as well as the hypothetical Fe(V) species in Rieske non-heme oxygenases, is orders of magnitude more stable than these other high-valence species in the absence of its primary substrate. It has recently been discovered that the bis-Fe(IV) intermediate exhibits a unique near-IR absorption feature which has been attributed to a novel charge-resonance phenomenon. This review compares the properties of MauG with structurally related enzymes, summarizes the current knowledge of this new high-valence iron intermediate, including its chemical origin and structural basis, explores the formation and consequences of charge resonance, and recounts the long-range catalytic mechanism in which bis-Fe(IV) participates. Biological strategies for storing oxidizing equivalents with iron ions are also discussed.

Diradical intermediate within the context of tryptophan tryptophylquinone biosynthesis

Co-reporter:J. Krzystek;Sooim Shin;Victor L. Davidson;Fange Liu;Lyndal M. R. Jensen;Carrie M. Wilmot;Erik T. Yukl

PNAS 2013 Volume 110 (Issue 12 ) pp:4569-4573

Publication Date(Web):2013-03-19

DOI:10.1073/pnas.1215011110

Despite the importance of tryptophan (Trp) radicals in biology, very few radicals have been trapped and characterized in a physiologically meaningful context. Here we demonstrate that the diheme enzyme MauG uses Trp radical chemistry to catalyze formation of a Trp-derived tryptophan tryptophylquinone cofactor on its substrate protein, premethylamine dehydrogenase. The unusual six-electron oxidation that results in tryptophan tryptophylquinone formation occurs in three discrete two-electron catalytic steps. Here the exact order of these oxidation steps in the processive six-electron biosynthetic reaction is determined, and reaction intermediates are structurally characterized. The intermediates observed in crystal structures are also verified in solution using mass spectrometry. Furthermore, an unprecedented Trp-derived diradical species on premethylamine dehydrogenase, which is an intermediate in the first two-electron step, is characterized using high-frequency and -field electron paramagnetic resonance spectroscopy and UV-visible absorbance spectroscopy. This work defines a unique mechanism for radical-mediated catalysis of a protein substrate, and has broad implications in the areas of applied biocatalysis and understanding of oxidative protein modification during oxidative stress.

Tryptophan-mediated charge-resonance stabilization in the bis-Fe(IV) redox state of MauG

Co-reporter:Jiafeng Geng;Kednerlin Dornevil;Victor L. Davidson

PNAS 2013 Volume 110 (Issue 24 ) pp:9639-9644

Publication Date(Web):2013-06-11

DOI:10.1073/pnas.1301544110

The diheme enzyme MauG catalyzes posttranslational modifications of a methylamine dehydrogenase precursor protein to generate a tryptophan tryptophylquinone cofactor. The MauG-catalyzed reaction proceeds via a bis-Fe(IV) intermediate in which one heme is present as Fe(IV)=O and the other as Fe(IV) with axial histidine and tyrosine ligation. Herein, a unique near-infrared absorption feature exhibited specifically in bis-Fe(IV) MauG is described, and evidence is presented that it results from a charge-resonance-transition phenomenon. As the two hemes are physically separated by 14.5 Å, a hole-hopping mechanism is proposed in which a tryptophan residue located between the hemes is reversibly oxidized and reduced to increase the effective electronic coupling element and enhance the rate of reversible electron transfer between the hemes in bis-Fe(IV) MauG. Analysis of the MauG structure reveals that electron transfer via this mechanism is rapid enough to enable a charge-resonance stabilization of the bis-Fe(IV) state without direct contact between the hemes. The finding of the charge-resonance-transition phenomenon explains why the bis-Fe(IV) intermediate is stabilized in MauG and does not permanently oxidize its own aromatic residues.

An unexpected copper catalyzed ‘reduction’ of an arylazide to amine through the formation of a nitrene intermediate

Co-reporter:Hanjing Peng, Kednerlin H. Dornevil, Alexander B. Draganov, Weixuan Chen, Chaofeng Dai, William H. Nelson, Aimin Liu, Binghe Wang

Tetrahedron 2013 69(25) pp: 5079-5085

Publication Date(Web):

DOI:10.1016/j.tet.2013.04.091

Pirin is an iron-dependent redox regulator of NF-κB

Co-reporter:Fange Liu;Shingo Esaki;Rong Fu;Vesna de Serrano;Lirong Chen;Imran Rehmani

PNAS 2013 Volume 110 (Issue 24 ) pp:9722-9727

Publication Date(Web):2013-06-11

DOI:10.1073/pnas.1221743110

Pirin is a nuclear nonheme Fe protein of unknown function present in all human tissues. Here we describe that pirin may act as a redox sensor for the nuclear factor κB (NF-κB) transcription factor, a critical mediator of intracellular signaling that has been linked to cellular responses to proinflammatory signals and controls the expression of a vast array of genes involved in immune and stress responses. Pirin’s regulatory effect was tested with several metals and at different oxidations states, and our spectroscopic results show that only the ferric form of pirin substantially facilitates binding of NF-κB proteins to target κB genes, a finding that suggests that pirin performs a redox-sensing role in NF-κB regulation. The molecular mechanism of such a metal identity- and redox state-dependent regulation is revealed by our structural studies of pirin. The ferrous and ferric pirin proteins differ only by one electron, yet they have distinct conformations. The Fe center is shown to play an allosteric role on an R-shaped surface area that has two distinct conformations based on the identity and the formal redox state of the metal. We show that the R-shaped area composes the interface for pirin-NF-κB binding that is responsible for modulation of NF-κB’s DNA-binding properties. The nonheme Fe protein pirin is proposed to serve as a reversible functional switch that enables NF-κB to respond to changes in the redox levels of the cell nucleus.

Chemical Rescue of the Distal Histidine Mutants of Tryptophan 2,3-Dioxygenase

Co-reporter:Jiafeng Geng ; Kednerlin Dornevil

Journal of the American Chemical Society 2012 Volume 134(Issue 29) pp:12209-12218

Publication Date(Web):June 28, 2012

DOI:10.1021/ja304164b

Tryptophan 2,3-dioxygenase (TDO) is a heme-dependent enzyme that catalyzes the oxidative degradation of l-tryptophan (l-Trp) to N-formylkynurenine (NFK). A highly conserved histidine residue in the distal heme pocket has attracted great attention in the mechanistic studies of TDO. However, a consensus has not been reached regarding whether and how this distal histidine plays a catalytic role after substrate binding. In this study, three mutant proteins, H72S, H72N, and Q73F were generated to investigate the function of the distal histidine residue in Cupriavidus metallidurans TDO (cmTDO). Spectroscopic characterizations, enzymatic kinetic analysis, and chemical rescue assays were employed to study the biochemical properties of the wild-type enzyme and the mutant proteins. Rapid kinetic methods were utilized to explore the molecular basis for the observed stimulation of catalytic activity by 2-methylimidazole in the His72 variants. The results indicate that the distal histidine plays multiple roles in cmTDO. First, His72 contributes to but is not essential for substrate binding. In addition, it shields the heme center from nonproductive binding of exogenous small ligand molecules (i.e., imidazole and its analogs) via steric hindrance. Most importantly, His72 participates in the subsequent chemical catalytic steps after substrate binding possibly by providing H-bonding interactions to the heme-bound oxygen.

Role of Calcium in Metalloenzymes: Effects of Calcium Removal on the Axial Ligation Geometry and Magnetic Properties of the Catalytic Diheme Center in MauG

Co-reporter:Yan Chen, Sunil G. Naik, J. Krzystek, Sooim Shin, William H. Nelson, Shenghui Xue, Jenny J. Yang, Victor L. Davidson, and Aimin Liu

Biochemistry 2012 Volume 51(Issue 8) pp:

Publication Date(Web):February 8, 2012

DOI:10.1021/bi201575f

MauG is a diheme enzyme possessing a five-coordinate high-spin heme with an axial His ligand and a six-coordinate low-spin heme with His-Tyr axial ligation. A Ca2+ ion is linked to the two hemes via hydrogen bond networks, and the enzyme activity depends on its presence. Removal of Ca2+ altered the electron paramagnetic resonance (EPR) signals of each ferric heme such that the intensity of the high-spin heme was decreased and the low-spin heme was significantly broadened. Addition of Ca2+ back to the sample restored the original EPR signals and enzyme activity. The molecular basis for this Ca2+-dependent behavior was studied by magnetic resonance and Mössbauer spectroscopy. The results show that in the Ca2+-depleted MauG the high-spin heme was converted to a low-spin heme and the original low-spin heme exhibited a change in the relative orientations of its two axial ligands. The properties of these two hemes are each different than those of the heme in native MauG and are now similar to each other. The EPR spectrum of Ca2+-free MauG appears to describe one set of low-spin ferric heme signals with a large gmax and g anisotropy and a greatly altered spin relaxation property. Both EPR and Mössbauer spectroscopic results show that the two hemes are present as unusual highly rhombic low-spin hemes in Ca2+-depleted MauG, with a smaller orientation angle between the two axial ligand planes. These findings provide insight into the correlation of enzyme activity with the orientation of axial heme ligands and describe a role for the calcium ion in maintaining this structural orientation that is required for activity.

Evidence for a Dual Role of an Active Site Histidine in α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase

Co-reporter:Lu Huo, Andrew J. Fielding, Yan Chen, Tingfeng Li, Hiroaki Iwaki, Jonathan P. Hosler, Lirong Chen, Yoshie Hasegawa, Lawrence Que Jr., and Aimin Liu

Biochemistry 2012 Volume 51(Issue 29) pp:

Publication Date(Web):July 2, 2012

DOI:10.1021/bi300635b

The previously reported crystal structures of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) show a five-coordinate Zn(II)(His)3(Asp)(OH2) active site. The water ligand is H-bonded to a conserved His228 residue adjacent to the metal center in ACMSD from Pseudomonas fluorescens (PfACMSD). Site-directed mutagenesis of His228 to tyrosine and glycine in this study results in a complete or significant loss of activity. Metal analysis shows that H228Y and H228G contain iron rather than zinc, indicating that this residue plays a role in the metal selectivity of the protein. As-isolated H228Y displays a blue color, which is not seen in wild-type ACMSD. Quinone staining and resonance Raman analyses indicate that the blue color originates from Fe(III)-tyrosinate ligand-to-metal charge transfer. Co(II)-substituted H228Y ACMSD is brown in color and exhibits an electron paramagnetic resonance spectrum showing a high-spin Co(II) center with a well-resolved 59Co (I = 7/2) eight-line hyperfine splitting pattern. The X-ray crystal structures of as-isolated Fe-H228Y (2.8 Å) and Co-substituted (2.4 Å) and Zn-substituted H228Y (2.0 Å resolution) support the spectroscopic assignment of metal ligation of the Tyr228 residue. The crystal structure of Zn–H228G (2.6 Å) was also determined. These four structures show that the water ligand present in WT Zn-ACMSD is either missing (Fe-H228Y, Co-H228Y, and Zn-H228G) or disrupted (Zn-H228Y) in response to the His228 mutation. Together, these results highlight the importance of His228 for PfACMSD’s metal specificity as well as maintaining a water molecule as a ligand of the metal center. His228 is thus proposed to play a role in activating the metal-bound water ligand for subsequent nucleophilic attack on the substrate.

Decarboxylation mechanisms in biological system

Co-reporter:Tingfeng Li, Lu Huo, Christopher Pulley, Aimin Liu

Bioorganic Chemistry 2012 Volume 43() pp:2-14

Publication Date(Web):August 2012

DOI:10.1016/j.bioorg.2012.03.001

This review examines the mechanisms propelling cofactor-independent, organic cofactor-dependent and metal-dependent decarboxylase chemistry. Decarboxylation, the removal of carbon dioxide from organic acids, is a fundamentally important reaction in biology. Numerous decarboxylase enzymes serve as key components of aerobic and anaerobic carbohydrate metabolism and amino acid conversion. In the past decade, our knowledge of the mechanisms enabling these crucial decarboxylase reactions has continued to expand and inspire. This review focuses on the organic cofactors biotin, flavin, NAD, pyridoxal 5′-phosphate, pyruvoyl, and thiamin pyrophosphate as catalytic centers. Significant attention is also placed on the metal-dependent decarboxylase mechanisms.Graphical abstractHighlights► Biological decarboxylation reactions use a wide range of approaches to weaken and cleave the CC bond. ► Both organic and inorganic cofactors are capable of serving as the catalytic center of decaroboxylases. ► Metal ions are found in both O2-dependent and oxidant-independent decarboxylase reactions.

Heme Iron Nitrosyl Complex of MauG Reveals an Efficient Redox Equilibrium between Hemes with Only One Heme Exclusively Binding Exogenous Ligands

Co-reporter:Rong Fu, Fange Liu, Victor L. Davidson and Aimin Liu

Biochemistry 2009 Volume 48(Issue 49) pp:

Publication Date(Web):November 13, 2009

DOI:10.1021/bi9017544

MauG is a diheme enzyme that oxidizes two protein-bound tryptophan residues to generate a catalytic tryptophan tryptophylquinone cofactor within methylamine dehydrogenase. Upon the two-electron oxidation of bis-ferric MauG, the two c-type hemes exist as a spin-uncoupled bis-Fe(IV) species with only one binding oxygen, which is chemically equivalent to a single ferryl heme plus a π porphyrin cation radical (Li, X. et al. (2008) Proc. Natl. Acad. Sci. U.S.A.105, 8597−8600). The EPR spectrum of the nitrosyl complex of fully reduced MauG shows a single six-coordinate Fe(II)-NO species, which is characteristic of a histidine-ligated Fe(II)-NO moiety in the heme environment. Exposure of partially reduced MauG to NO reveals a redox equilibrium with facile electron transfer between hemes but with only one binding nitric oxide. Thus, the second heme is able to stabilize all three redox states of iron (Fe(II), Fe(III), and Fe(IV)) in a six-coordinate protein-bound heme without binding exogenous ligands. This is unprecedented behavior for a protein-bound heme for which each of these redox states is relevant to the overall catalytic mechanism. The results also illustrate the electronic communication between the two iron centers, which function as a diheme unit rather than independent heme cofactors.

The roles of Rhodobacter sphaeroides copper chaperones PCuAC and Sco (PrrC) in the assembly of the copper centers of the aa3-type and the cbb3-type cytochrome c oxidases

Co-reporter:Audie K. Thompson, Jimmy Gray, Aimin Liu, Jonathan P. Hosler

Biochimica et Biophysica Acta (BBA) - Bioenergetics (June 2012) Volume 1817(Issue 6) pp:955-964

Publication Date(Web):June 2012

DOI:10.1016/j.bbabio.2012.01.003

Heme-dependent dioxygenases in tryptophan oxidation

Co-reporter:Jiafeng Geng, Aimin Liu

Archives of Biochemistry and Biophysics (15 February 2014) Volume 544() pp:18-26

Publication Date(Web):15 February 2014

DOI:10.1016/j.abb.2013.11.009