Fast Product Formation and Slow Product Release Are Important Features in a Hysteretic Reaction Mechanism of Glutathione Transferase T2-2†

Biochemistry ◽  
1999 ◽  
Vol 38 (31) ◽  
pp. 9982-9991 ◽  
Author(s):  
Per Jemth ◽  
Bengt Mannervik
Keyword(s):  
Reaction Mechanism ◽  
Glutathione Transferase ◽  
Product Formation ◽  
Product Release

A computational study to unravel the selectivity in an iron-catalysed [3 + 2] cycloaddition of aziridine and heterocumulenes

RSC Advances ◽  
2015 ◽  
Vol 5 (115) ◽  
pp. 95379-95384 ◽  
Author(s):  
Debashis Adhikari
Keyword(s):  
Reaction Mechanism ◽  
Computational Study ◽  
Product Formation ◽  
Iron Salts

The reaction mechanism of cycloaddition between phenyl aziridine and heterocumulene catalysed by iron salts in water has been modeled computationally to trace the origin of excellent regioselectivity toward 5-substituted product formation.

Cycloaddition Reactions of Substituted Allenes with Triplet Excited Aromatic Thiones: Product Formation and Reaction Mechanism

1985 ◽  
Vol 26 (2) ◽  
pp. 120-130 ◽  
Author(s):  
J. Kamphuis ◽  
P.D.J. Grootenhuis ◽  
A.P. Ruijter ◽  
R.G. Visser ◽  
H.J.T. Bos
Keyword(s):  
Reaction Mechanism ◽  
Product Formation ◽  
Cycloaddition Reactions

Valine 10 May Act as a Driver for Product Release from the Active Site of Human Glutathione Transferase P1-1†,‡

Biochemistry ◽  
2000 ◽  
Vol 39 (51) ◽  
pp. 15961-15970 ◽  
Author(s):  
Chiara Micaloni ◽  
Anna P. Mazzetti ◽  
Marzia Nuccetelli ◽  
Jamie Rossjohn ◽  
William J. McKinstry ◽  
...  
Keyword(s):  
Active Site ◽  
Glutathione Transferase ◽  
Product Release

scholarly journals A metal ion orients mRNA to ensure accurate 2’-O ribosyl methylation of the first nucleotide of the SARS-CoV-2 genome

2021 ◽  
Author(s):  
Thiruselvam Viswanathan ◽  
Anurag Misra ◽  
Siu-Hong Chan ◽  
Shan Qi ◽  
Nan Dai ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Metal Ion ◽  
Immune Surveillance ◽  
Binding Mode ◽  
Product Formation ◽  
Structural Basis ◽  
Outbreak Strain ◽  
Product Release ◽  
The Status ◽  
Divalent Metal Ion

AbstractThe SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2’-OH of the first transcribed nucleotide of the viral mRNA by covalently attaching a methyl group to it. The 2’-O methylation of the first nucleotide converts the status of mRNA cap from Cap-0 to Cap-1, and thus, helps the virus evade immune surveillance in the host cell. Here, we report two structures of nsp16/nsp10 representing pre- and post-release states of the RNA product (Cap-1). We observe overall widening of the enzyme upon product formation, and an inward twisting motion in the substrate binding region upon product release. These conformational changes reset the enzyme for the next round of catalysis. The structures also identify a unique binding mode and the importance of a divalent metal ion for 2’-O methylation. We also describe underlying structural basis for the perturbed enzymatic activity of a clinical variant of SARS-CoV-2, and a previous SARS-CoV outbreak strain.

scholarly journals Glutamate-64, a newly identified residue of the functionally conserved electron-sharing network contributes to catalysis and structural integrity of glutathione transferases

2007 ◽  
Vol 402 (2) ◽  
pp. 339-348 ◽  
Author(s):  
Pakorn Winayanuwattikun ◽  
Albert J. Ketterman
Keyword(s):  
Structural Integrity ◽  
Glutathione Transferase ◽  
Product Formation ◽  
Glutathione Transferases ◽  
Nucleophilic Attack ◽  
Anopheles Dirus ◽  
Catalytic Function ◽  
Equivalent Residue ◽  
Vitro Analysis

In Anopheles dirus glutathione transferase D3-3, position 64 is occupied by a functionally conserved glutamate residue, which interacts directly with the γ-glutamate moiety of GSH (glutathione) as part of an electron-sharing network present in all soluble GSTs (glutathione transferases). Primary sequence alignment of all GST classes suggests that Glu64 is one of a few residues that is functionally conserved in the GST superfamily. Available crystal structures as well as consideration of the property of the equivalent residue at position 64, acidic or polar, suggest that the GST electron-sharing motif can be divided into two types. Electrostatic interaction between the GSH glutamyl and carboxylic Glu64, as well as with Arg66 and Asp100, was observed to extend the electron-sharing motif identified previously. Glu64 contributes to the catalytic function of this motif and the ‘base-assisted deprotonation’ that are essential for GSH ionization during catalysis. Moreover, this residue also appears to affect multiple steps in the enzyme catalytic strategy, including binding of GSH, nucleophilic attack by thiolate at the electrophilic centre and product formation, probably through active-site packing effects. Replacement with non-functionally-conserved amino acids alters initial packing or folding by favouring aggregation during heterologous expression. Thermodynamic and reactivation in vitro analysis indicated that Glu64 also contributes to the initial folding pathway and overall structural stability. Therefore Glu64 also appears to impact upon catalysis through roles in both initial folding and structural maintenance.

Unraveling the Mechanism of Tricyclic Bis-spiroketal Formation from Diyne Diol by DFT Study

2019 ◽  
Vol 16 (5) ◽  
pp. 392-395
Author(s):  
Kamlesh Sharma
Keyword(s):  
Density Functional Theory ◽  
Reaction Mechanism ◽  
Dft Calculations ◽  
Density Functional ◽  
Activation Parameters ◽  
Product Formation ◽  
Ring Closure ◽  
Reaction Pathways ◽  
Enol Ether ◽  
Functional Theory

The mechanism of addition of nucleophiles to the π-acid complexed alkynes has been studied successfully by the assessment of energy of intermediates and activation parameters. To elucidate the origin of stereoselectivity and predict the reaction pathways, the geometry optimizations of reactants, products, intermediates and transition states, were calculated by using density functional theory (DFT) at the B3LYP/6-31+G(d) method. The reaction mechanism of hydration of alkynes in the catalyzed synthesis of bis-spiroketal by DFT calculations is explored. The pyranyl enol ether was formed regioselectively by the first ring closure. Further, bis-enol ether was formed by second 6-exodig addition. Then, dehydration, followed by dehydrative ring closure finally gave bis-spiroketal product. It is concluded that one of the most feasible reaction pathways comprises pyranyl enol ether and bis-enol ether formation as intermediates. The final cyclization step of product formation is endothermic. In terms of stereochemistry, the trans-product is found to be energetically more stable than cisproduct and hence supports the electivity of the reaction.

scholarly journals Reaction mechanism of the farnesyl pyrophosphate C-methyltransferase towards the biosynthesis of pre-sodorifen pyrophosphate by Serratia plymuthica 4Rx13

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie Chantal Lemfack ◽  
Wolfgang Brandt ◽  
Katja Krüger ◽  
Alexandra Gurowietz ◽  
Jacky Djifack ◽  
...  
Keyword(s):  
Amino Acids ◽  
Reaction Mechanism ◽  
Hydrolysis Product ◽  
Binding Pocket ◽  
Product Formation ◽  
Site Directed Mutagenesis ◽  
Terpene Biosynthesis ◽  
Serratia Plymuthica ◽  
Hydrophobic Binding ◽  
Prenyl Pyrophosphate

AbstractClassical terpenoid biosynthesis involves the cyclization of the linear prenyl pyrophosphate precursors geranyl-, farnesyl-, or geranylgeranyl pyrophosphate (GPP, FPP, GGPP) and their isomers, to produce a huge number of natural compounds. Recently, it was shown for the first time that the biosynthesis of the unique homo-sesquiterpene sodorifen by Serratia plymuthica 4Rx13 involves a methylated and cyclized intermediate as the substrate of the sodorifen synthase. To further support the proposed biosynthetic pathway, we now identified the cyclic prenyl pyrophosphate intermediate pre-sodorifen pyrophosphate (PSPP). Its absolute configuration (6R,7S,9S) was determined by comparison of calculated and experimental CD-spectra of its hydrolysis product and matches with those predicted by semi-empirical quantum calculations of the reaction mechanism. In silico modeling of the reaction mechanism of the FPP C-methyltransferase (FPPMT) revealed a SN2 mechanism for the methyl transfer followed by a cyclization cascade. The cyclization of FPP to PSPP is guided by a catalytic dyad of H191 and Y39 and involves an unprecedented cyclopropyl intermediate. W46, W306, F56, and L239 form the hydrophobic binding pocket and E42 and H45 complex a magnesium cation that interacts with the diphosphate moiety of FPP. Six additional amino acids turned out to be essential for product formation and the importance of these amino acids was subsequently confirmed by site-directed mutagenesis. Our results reveal the reaction mechanism involved in methyltransferase-catalyzed cyclization and demonstrate that this coupling of C-methylation and cyclization of FPP by the FPPMT represents an alternative route of terpene biosynthesis that could increase the terpenoid diversity and structural space.

scholarly journals Spectroscopic Investigation of Degradation Reaction Mechanism in γ-Rays Irradiation of HDPE

2020 ◽  
Vol 11 (2) ◽  
pp. 9405-9419
Keyword(s):  
Reaction Mechanism ◽  
Chain Scission ◽  
Product Formation ◽  
X Ray Diffraction ◽  
Γ Irradiation ◽  
Ketone Carbonyl ◽  
Degradation Reaction ◽  
Γ Rays ◽  
Xrd Techniques ◽  
Dose Dependent

Radiation damage and reaction mechanism of product formation due to γ-irradiation in high-density polyethylene (HDPE) have been studied by Fourier transform infrared (FTIR), UV-vis spectroscopic, and x-ray diffraction (XRD) techniques. A Co60gamma source (with a dose rate of 1.707 kGy/hr) has been used up to the total dose of 570 kGy. There are dose-dependent changes in the polymer. The optical band gap decreases with the increase of the γ-irradiation dose. Formations of unsaturation centers have been observed. FTIR observed that a lower dose of γ-irradiation induces the formation of an unsaturated (-C=C-) group and a ketone carbonyl group. Breaking of the C-H bond is more frequent than the breaking of the C-C bond in irradiated HDPE. Crosslinking dominates over chain scission (breaking of C-C bond of the main chain) at a lower dose (100 kGy). There has been no significant influence of γ-irradiation on the crystalline structure, although crystalline size decreases. Mechanisms of the formation of alkyl, allylic, and polyenyl radicals have been investigated.

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