Mechanistic insights into the γ-elimination reaction of l-methionine catalyzed by methionine γ-lyase (MGL)

Lin, Beibei; Liu, Yongjun

doi:10.1007/s00214-017-2140-9

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…In the transamination reaction, the two proton transfer steps play a key role for the formation and cleavage of two C–N bonds. Such PLP hydroxyl group assisted proton transfer has also occurred in some other PLP-dependent enzymes. − In general, the formation of the external aldimine of IM4 is endothermic by 8.9 kcal/mol.…”

Section: Resultsmentioning

confidence: 96%

“…According to our calculation results, the deprotonation of Cα (step 5) corresponds to an energy barrier of 17.4 kcal/mol and is considered to be rate-limiting, which is consistent with the PLP-dependent ω-transaminase and methionine γ-lyase. 51,52 Then, we performed an electrostatic analysis of eight surrounding residues (Figure S6) toward this step (IM4 → IM5). The influence of residue i on the energy barrier can be described as ΔE i−0 = ΔE i − ΔE 0 , in which ΔE i is the energy barrier when the charge on residue i was set to 0, ΔE 0 is the original energy barrier, and ΔE i−0 indicates the change of the energy barrier caused by the electrostatic interaction of residue i. ΔE i−0 > 0 means residue i lowers the energy barrier, while ΔE i−0 < 0 is exactly the opposite.…”

Section: Residue Electrostatic Analysismentioning

confidence: 99%

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Catalytic Mechanism of Pyridoxal 5′-Phosphate-Dependent Aminodeoxychorismate Lyase: A Computational QM/MM Study

Dong

Liu

2023

J. Chem. Inf. Model.

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Aminodeoxychorismate lyase (ADCL) is a kind of pyridoxal-5′phosphate (PLP)-dependent enzyme that catalyzes the conversion of 4-amino-4deoxychorismate (ADC) to p-aminobenzoate (PABA), which is a key step for the biosynthesis of folate. To illuminate the reaction details at the atomistic level, an enzyme−substrate reactant model has been constructed, and QM/MM calculations have been performed. Our calculation results reveal that the overall catalytic cycle contains 11 elementary steps, which can be described by three stages, including the transamination reaction of PLP, the release of pyruvate and aromatization of ADC, and the recovery to the initial aldimine. During the reaction, a series of intramolecular proton transfer are involved, which are the key for the C−N bond formation and cleavage as well as the aromatization of the ADC ring. In addition to forming the Schiff base with the pocket residue Lys251 and substrate in the internal aldimine and the external aldimine, respectively, the coenzyme PLP also plays a critical role in the intramolecular proton transfer by employing its hydroxyl oxygen anion and phosphate group. These findings may provide useful information for further understanding the catalytic mechanism of other PLP-dependent enzymes.

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Section: Resultsmentioning

confidence: 96%

Section: Residue Electrostatic Analysismentioning

confidence: 99%

Catalytic Mechanism of Pyridoxal 5′-Phosphate-Dependent Aminodeoxychorismate Lyase: A Computational QM/MM Study

Dong

Liu

2023

J. Chem. Inf. Model.

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“…In our previous study, we were able to find a novel source of L-Methionase, the fungi, Aspergillus Fumigatus which demonstrated effective anticancer properties. Other bacteria reported to produce L-Methionase include Citrobacter freundii [12], Brevibacterium lines [13], Clostridium sporogenes [14], Streptomyces sp [15] [11]. The aim of this study of isolate, screen, and identify L-Methionase from rotten fruits and vegetables by promising isolate from anticancer application.…”

Section: Discussionmentioning

confidence: 99%

Isolation, Screening And Morphological Identification Of Fungal L-Methionase From Rotten Fruits And Vegetables

Rajpara,

Vadhiya,

Kava

et al. 2024

eatp

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Globally, cancer is becoming a more common cause of both mortality and morbidity. L-Methionase is one of the few microbial enzymes with high therapeutic value since it has been reported as an effective anticancer agent against many types of tumor cell lines like breast, lung, colon, kidney, and glioblastoma. Normal cells have a high requirement of amino acids as nutrients, without amino acids, tumor cells fail to function because protein can't be synthesized and tumor cells will die. L-Methionase has important biotechnological applications because of exhibits hydrolytic properties to catalyze α-γ elimination of L-methionine, an essential amino acid to α-ketobutyrate, methanethiol, and ammonia. The catalytic activity of L-Methionase could be used as enzyme supplementation therapy for these diseases. enzyme has been extensively studied by a wide range of organisms, including bacteria, fungi, protozoa, and plants. As a result, of the current study, we obtain 24 fungal isolates from rotten fruits and vegetables. Qualitative and quantitative screening assay test shows the ability of seven isolates to grow with yellow zones surrounding their colonial growth. MFL 9 (3.45 µmol/min/ml) and MFL24 (2.95 µmol/min/ml) exhibit the highest L-Methionase enzyme activity according to the Nesslerization assay performed for the detection of ammonia. Therefore, the current study indicates that the enzyme extract from the new isolates has enhanced L-Methionase activity and could be a novel and promising therapy for cancer.

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“…Vitamins play several important metabolic roles including in catalysis and receptor binding . For example, vitamin B 6 (pyridoxal-5′-phosphate) is important in Schiff base enzymatic catalysis, while vitamin D 3 binds to receptors involved in bone and calcium metabolism . Due to their insufficient production within the cell, vitamins must be obtained via our diets .…”

Section: Introductionmentioning

confidence: 99%

Multiscale Computational Study on the Catalytic Mechanism of the Nonmetallo Amidase Maleamate Amidohydrolase (NicF)

2019

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Maleamate amidohydrolase (NicF) is a key enzyme in vitamin B 3 metabolism that catalyzes the hydrolysis of maleamate to produce maleic acid and ammonia. Unlike most members from the amidohydrolase superfamily it does not require a metal ion. Here, we use multiscale computational enzymology to investigate the catalytic mechanism, substrate binding, oxyanion hole, and roles of key active site residues of NicF from Bordetella bronchiseptica. In particular, molecular dynamics (MD) simulations, quantum mechanics/molecular mechanics (QM/MM) and QTAIM methods have been applied. The mechanism of the NicF-catalyzed reaction proceeds by a nucleophilic addition−elimination sequence involving the formation of a thioester enzyme intermediate (IC2 in stage 1) followed by hydrolysis of the thioester bond to form the products (stage 2). Consequently, the formation of IC2 in stage 1 is the rate-limiting step with a barrier of 88.8 kJ•mol −1 relative to the reactant complex, RC. Comparisons with related metal-dependent enzymes, particularly the zinc-dependent nicotinamidase from Streptococcus pneumonia (SpNic), have also been made to further illustrate unique features of the present mechanism. Along with −NH− donor groups of the oxyanion hole (i.e., HN−Thr146, HN−Cys150), the active site β-hydroxyl of threonine (HO−βThr146) is concluded to play a role in stabilizing the carbonyl oxygen of maleamate during the mechanism.

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Mechanistic insights into the γ-elimination reaction of l-methionine catalyzed by methionine γ-lyase (MGL)

Cited by 7 publications

References 35 publications

Catalytic Mechanism of Pyridoxal 5′-Phosphate-Dependent Aminodeoxychorismate Lyase: A Computational QM/MM Study

Catalytic Mechanism of Pyridoxal 5′-Phosphate-Dependent Aminodeoxychorismate Lyase: A Computational QM/MM Study

Isolation, Screening And Morphological Identification Of Fungal L-Methionase From Rotten Fruits And Vegetables

Multiscale Computational Study on the Catalytic Mechanism of the Nonmetallo Amidase Maleamate Amidohydrolase (NicF)

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