Aimin Liu

Aimin Liu
University of Texas at San Antonio | UTSA · Department of Chemistry

Ph.D.

About

125
Publications
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2,821
Citations
Additional affiliations
January 2016 - present
University of Texas at San Antonio
Position
  • Chair

Publications

Publications (125)
Article
Full-text available
Aldehydes are ubiquitous intermediates in metabolic pathways, and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation which can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathwa...
Article
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,...
Article
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 va...
Article
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, premethylamin...
Article
High-valent iron species are powerful oxidizing agents in chemical and biological catalysis. The best characterized form of an Fe(V) equivalent described in biological systems is the combination of a b-type heme with Fe(IV)=O and a porphyrin or amino acid cation radical (termed Compound I). This work describes an alternative natural mechanism to st...
Article
Here, the choice of the first coordination shell of the metal center is analyzed from the perspective of charge maintenance in a binary enzyme–substrate complex and an O2-bound ternary complex in the nonheme iron oxygenases. Comparing homogentisate 1,2-dioxygenase and gentisate dioxygenase highlights the significance of charge maintenance after sub...
Article
Mononuclear, nonheme iron enzymes are known for their ability to mediate the oxidation of organic molecules in primary and secondary metabolism. One class of such enzymes is the diol dioxygenases that catalyze the oxidative cleavage of aromatic molecules. They come in two varieties, intradiol and extradiol, that add molecular oxygen symmetrically o...
Chapter
Carotenoids are a family of pigment compounds, a subset of which are precursors for vitamin A biosynthesis. These pigments are derived from isopentenyl pyrophosphate (IPP), with geranylgeranyl diphosphate being the first metabolite unique to carotenoid biosynthesis in plants, algae, fungi, some bacteria, and arthropods. This chapter highlights the...
Article
Two histidine-ligated heme-dependent monooxygenase proteins, TyrH and SfmD, have recently been found to resemble enzymes from the dioxygenase superfamily currently named after tryptophan 2,3-dioxygenase (TDO), that is, the TDO superfamily. These latest findings prompted us to revisit the structure and function of the superfamily. The enzymes in thi...
Article
Full-text available
Cysteamine dioxygenase (ADO) plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis in humans by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate. However, as the only thiol dioxygenase that processes both small-molecule and pr...
Article
Few articles are reported for the simultaneous separation and sensitive detection of the kynurenine pathway (KP) metabolites. This work describes a capillary electrochromatography-mass spectrometry (CEC-MS) method using acrylamido-2-methyl-1-propanesulfonic acid (AMPS) functionalized stationary phase. The AMPS column was prepared by first performin...
Article
A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by a de novo crystal structural and spectroscopic study: SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78 Å resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor attac...
Article
The heme-dependent l-tyrosine hydroxylases (TyrHs) in natural product biosynthesis constitute a new enzyme family in contrast to the nonheme iron enzymes for DOPA production. A representative TyrH exhibits dual reactivity of C-H and C-F bond cleavage when challenged with 3-fluoro-l-tyrosine (3-F-Tyr) as a substrate. However, little is known about h...
Article
Full-text available
SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78-Å resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor attached to the protein with an unusual HxnHxxxC motif (n ~ 38). This heme cofactor is unique in two aspects. It contains a single thioether bond in a cysteine–vinyl...
Article
Full-text available
HupZ is an expected heme degrading enzyme in the heme acquisition and utilization pathway in Group A Streptococcus. The isolated HupZ protein containing a C-terminal V5-His6 tag exhibits a weak heme degradation activity. Here, we revisited and characterized the HupZ-V5-His6 protein via biochemical, mutagenesis, protein quaternary structure, UV–vis,...
Article
In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, α-amino-β-carboxymuconate-ε-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (AC...
Article
Galactose oxidase (GAO) contains a Cu(II)-ligand radical cofactor. The cofactor, which is autocatalytically generated through the oxidation of the copper, consists of a cysteine-tyrosine radical (Cys-Tyr•) as a copper ligand. The formation of the crosslinked thioether bond is accompanied by a C-H bond scission on Tyr272 with few details known thus...
Article
Significance NAD ⁺ plays a critical role in redox-linked biological reactions as a cofactor or substrate. The knowledge of its de novo biosynthesis in mammals and certain bacteria is incomplete due to missing information of a nonheme iron dioxygenase mechanism and the conformation of its product that nonenzymatically produces the universal NAD ⁺ pr...
Article
The first step of the kynurenine pathway for L-tryptophan (L-Trp) degradation is catalyzed by heme-dependent dioxygenases, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). In this work, we employed stopped-flow optical absorption spectroscopy to study the kinetic behavior of the Michaelis complex of Cupriavidus metallidurans...
Article
Full-text available
Cysteamine dioxygenase (ADO) has been reported to exhibit two distinct biological functions with a non-heme iron center. It catalyzes oxidation of both cysteamine in sulfur metabolism and N-terminal cysteine-containing proteins or peptides, such as regulator of G protein signaling 5 (RGS5). It thereby preserves oxygen homeostasis in a variety of ph...
Article
Fluorochemicals are a widely distributed class of compounds and have been utilized across a wide range of industries for decades. Given the environmental toxicity and adverse health threats of some fluorochemicals, the development of new methods for their decomposition is significant to public health. However, the carbon–fluorine (C–F) bond is amon...
Article
CYP121 is a P450 enzyme from Mycobacterium tuberculosis that catalyzes a C-C coupling reaction between the two aromatic rings on its native substrate cyclo(L-Tyr-L-Tyr) (cYY) to form mycocyclosin, a necessary product for cell survival. Unlike the typical P450 enzymes for hydroxylation, CYP121 is believed to behave like a peroxidase and conduct radi...
Article
Full-text available
α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays an important role in L-tryptophan degradation via the kynurenine pathway. ACMSD forms a homodimer and is functionally inactive as a monomer because its catalytic assembly requires an arginine residue from a neighboring subunit. However, how the oligomeric state and self-associatio...
Article
Extradiol dioxygenases are essential biocatalysts to breakdown catechols. The vicinal oxygen chelate (VOC) superfamily contains a large number of extradiol dioxygenases, most of which are found as part of catabolic pathways degrading a variety of natural and human-made aromatic rings. However, the VOC also contains an emerging class of biosynthetic...
Article
LmbB2 is a peroxygenase-like enzyme that hydroxylates L-tyrosine to L-3,4-dihydroxyphenylalanine (DOPA) in the presence of hydrogen peroxide. However, its heme cofactor is ligated by a proximal histidine, not cysteine. We show that LmbB2 can oxidize L-tyrosine analogs with ring-deactivated substituents such as 3-nitro-, fluoro-, chloro-, iodo-L-tyr...
Article
Cysteine dioxygenase (CDO) is a non-heme iron enzyme that adds two oxygen atoms from dioxygen to the sulfur atom of L-cysteine. Adjacent to the iron site of mammalian CDO, a post-translationally generated Cys-Tyr cofactor is present, whose presence substantially enhances the oxygenase activity. The formation of the Cys-Tyr cofactor in CDO is an aut...
Article
Full-text available
Cysteine dioxygenase (CDO) plays an essential role in sulfur metabolism by regulating homeostatic levels of cysteine. Human CDO contains a post-translationally generated Cys93–Tyr157 cross-linked cofactor. Here, we investigated this Cys–Tyr cross-linking by incorporating unnatural tyrosines in place of Tyr157 via a genetic method. The catalytically...
Article
Treatment of both [CoCl( tBuPNP)] and [NiCl( tBuPNP)] ( tBuPNP = anion of 2,5-bis((di- tert-butylphosphino)methyl)pyrrole) with one equivalent of benzoquinone affords the corresponding chloride complexes containing a dehydrogenated PNP ligand, tBudPNP ( tBudPNP = anion of 2,5-bis((di- tert-butylphosphino)methylene)-2,5-dihydropyrrole). Dehydrogenat...
Preprint
3-Hydroxyanthranilate 3,4-dioxygenase (HAO) is an iron-dependent protein that activates O2 and inserts both O atoms into 3-hydroxyanthranilate (3-HAA). An intriguing question is how HAO can rapidly bind O2, even though local O2 concentrations and diffusion rates are relatively low. Here, a close inspection of the HAO structures revealed that substr...
Article
Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by ambiguity as to whether or not it possesses an anticipated protein‐derived cofactor. Herein, we report the discovery and elucidation of a Cys‐Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C‐S) bond. By genetically incorporat...
Article
Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by ambiguity as to whether or not it possesses an anticipated protein‐derived cofactor. Herein, we report the discovery and elucidation of a Cys‐Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C‐S) bond. By genetically incorporat...
Article
Full-text available
The kynurenine pathway is the primary route for L-tryptophan degradation in mammals. Intermediates and side products of this pathway are involved in immune response and neurodegenerative diseases. This makes the study of enzymes, especially those from mammalian sources, of the kynurenine pathway worthwhile. Recent studies on a bacterial version of...
Article
Heme-based tryptophan dioxygenases are established immunosuppressive metalloproteins with significant biomedical interest. Here, we synthesized two mechanistic probes to specifically test if the α-amino group of the substrate directly participates in a critical step of the O-atom transfer during catalysis in human tryptophan 2,3-dioxygenase (TDO)....
Article
Tryptophan-based free radicals have been implicated in a myriad of catalytic and electron transfer reactions in biology. However, very few of them have been trapped so that biophysical characterizations can be performed in a high precision context. In this work, tryptophan derivative-based radicals were studied by high-frequency/high-field electron...
Article
The di-heme enzyme, MauG, utilizes a high-valent, charge-resonance stabilizedbis-Fe(IV) state to perform protein radical-based catalytic chemistry. Though thebis-Fe(IV) species is able to oxidize remote tryptophan residues on its substrate protein, it does not rapidly oxidize its own residues in the absence of substrate. The slow return ofbis-Fe(IV...
Article
CYP121 is a cytochrome P450 enzyme from Mycobacterium tuberculosis that catalyzes the formation of a C-C bond between the aromatic groups of its cyclodityrosine substrate (cYY). The crystal structure of CYP121 in complex with cYY reveals that the solvent-derived ligand remains bound to the ferric ion in the enzyme-substrate complex. Whereas in the...
Article
CYP121 is a cytochrome P450 enzyme from Mycobacterium tuberculosis that catalyzes the formation of a C-C bond between the aromatic groups of its cyclodityrosine substrate (cYY). The crystal structure of CYP121 in complex with cYY reveals that the solvent-derived ligand remains bound to the ferric ion in the enzyme-substrate complex. Whereas in the...
Article
Full-text available
KatG is a bifunctional, heme-dependent enzyme in the front-line defense of numerous bacterial and fungal pathogens against H2O2-induced oxidative damage from host immune responses. Contrary to the expectation that catalase and peroxidase activities should be mutually antagonistic, peroxidatic electron donors (PxEDs) enhance KatG catalase activity....
Article
The di-heme enzyme, MauG, utilizes a high-valent, charge-resonance stabilized bis-Fe(IV) state to perform protein radical-based catalytic chemistry. Though the bis-Fe(IV) species is able to oxidize remote tryptophan residues on its substrate protein, it does not rapidly oxidize its own residues in the absence of substrate. The slow return of bis-Fe...
Article
Full-text available
CYP121, the P450 enzyme in Mycobacterium tuberculosis that catalyzes a sinle intramolecular C-C crosslinkin reaction in the biosynthesis of mycocyclosin, is crucial for the viability of this pathoen. This C-C couplin reaction represents an expansion of the activities carried out by P450 enzymes distinct from oxyen insertion. While the traditional m...
Article
In this report we describe the first human case of hypertryptophanemia confirmed to be due to tryptophan 2,3-dioxygenase deficiency. The underlying etiology was established by sequencing the TDO2 gene, in which there was compound heterozygosity for two rare variants: c.324G > C, p.Met108Ile and c.491dup, p.Ile165Aspfs*12. The pathogenicity of these...
Article
The diheme enzyme MauG utilizes H2O2 to perform oxidative posttranslational modification on a protein substrate. A bis-Fe(IV) species of MauG was previously identified as a key intermediate in this reaction. Heterolytic cleavage of the O-O bond of H2O2 drives the formation of the bis-Fe(IV) intermediate. In this work, we tested a hypothesis that a...
Article
Molecular oxygen is utilized in numerous metabolic pathways fundamental for life. Mononuclear nonheme iron-dependent oxygenase enzymes are well known for their involvement in some of these pathways, activating O2 so that oxygen atoms can be incorporated into their primary substrates. These reactions often initiate pathways that allow organisms to u...
Article
Full-text available
Aldehyde dehydrogenase typically perform oxidation of aldehydes to their corresponding carboxylic acid while reducing NAD(P)+ to NAD(P)H via covalent catalysis mediated by an active-site cysteine residue. One member of this superfamily, the enzyme 2-aminomuconate-6-semialdehyde dehydrogenase (AMSDH), is a component of the kynurenine pathway which c...
Article
Full-text available
The kynurenine pathway has received increasing attention as its connection to inflammation, the immune system and neurological conditions has become more apparent. It is the primary route for tryptophan catabolism in the liver and the starting point for the synthesis of nicotinamide adenine dinucleotide in mammals. Dysregulation or overactivation o...
Article
Full-text available
Plants synthesize carotenoids, which are essential for plant development and survival. These metabolites also serve as essential nutrients for human health. The biosynthetic pathway for all plant carotenoids occurs in chloroplasts and other plastids and requires 15-cis-[zeta]-carotene isomerase (Z-ISO). It was not known whether Z-ISO catalyzes isom...
Article
A Spare Tire to the Catalytic Metal: The Rubredoxin Iron in an Extradiol Dioxygenase: The rubredoxin motif is present in over 74,000 protein sequences and 2,000 structures, but few have known functions. A secondary, non-catalytic, rubredoxin-like iron site is conserved in 3-hydroxyanthranilate 3,4-dioxygenase (HAO), from single-cellular sources b...
Article
The biosynthesis of tryptophan tryptophylquinone, a protein-derived cofactor, involves a long-range reaction mediated by a bis-Fe(IV) intermediate of a di-heme 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 che...
Article
Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase determines the fate of tryptophan metabolites in the kynurenine pathway by controlling the quinolinate levels for de novo nicotinamide adenine dinucleotide biosynthesis. The unstable nature of its substrate has made gaining insight into its reaction mechanism difficult. Our electron param...
Article
Full-text available
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 ch...
Article
The amidohydrolase superfamily is a structure‐based cluster of enzymes that contain a sturdy and versatile triosephosphate isomerase (TIM)‐like (β/α)8‐barrel fold embracing the catalytic active site. To date, the amidohydrolase superfamily has grown into one of the largest families of enzymes, with tens of thousand of members catalysing a wide rang...
Article
"Quinolinic acid (QA)", a metabolite of the kynurenine pathway (KP), is implicated as a major neurological biomarker, which causes inflammatory disorders, whereas there is an increase evidence of the role of picolinic acid (PA) in neuroinflammation. Therefore, there is an urgent need to develop new clinical test for early diagnosis of neuroinflamma...
Chapter
Heme (iron protoporphyrin IX) proteins play important roles in a wide array of biological functions, including single electron transfer mediation, oxygen transport and storage, redox reactions, detoxification, and transcription regulation. Heme proteins are also known to play a key role in many metabolic processes involving oxidation reactions to s...
Article
Full-text available
Although the crystal structure of α-amino-β-carboxymuconate-ϵ-semialdehyde decarboxylase from Pseudomonas fluorescens was solved as a dimer, this enzyme is a mixture of monomer, dimer, and higher order structures in solution. In this work, we found that the dimeric state, not the monomeric state, is the functionally active form. Two conserved argin...
Chapter
Cell signaling and transcription is a tightly regulated process, integrating the activities of multiple interlinked pathways to respond in a precise manner to changes in the cellular environment. Many pathological conditions can be traced to defects in one or more of these regulatory mechanisms, which illustrates the requirement for exactness in wh...
Article
This article describes the development of a reliable CZE-ESI-MS method to simultaneously separate and quantitate three specific metabolites (3-hydroxyanthranilic acid (3-HAA), quinolinc acid (QA), and picolinic acid (PA)) of the kynurenine pathway (KP) of tryptophan catabolism. Using a covalently bonded sulfonated capillary. the parameters such as...
Article
MauG catalyzes posttranslational modifications of methylamine dehydrogenase to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. MauG possesses a five-coordinate high-spin and a six-coordinate low-spin ferric heme, the latter with His-Tyr ligation. Replacement of this tyrosine with lysine generates a MauG...
Article
The diheme enzyme MauG catalyzes a six-electron oxidation required for posttranslational modification of a precursor of methylamine dehydrogenase (preMADH) to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. Crystallographic studies had shown that Pro107, which resides in the distal pocket of the high-sp...
Article
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 Ca(2+) ion is linked to the two hemes via hydrogen bond networks, and the enzyme activity depends on its presence. Removal of Ca(2+) altered the electron paramagnetic resonance (EPR) signals...