Active Site Dynamical Effects in the Hydrogen Transfer Rate-limiting Step in the Catalysis of Linoleic Acid by Soybean Lipoxygenase-1 (SLO-1): Primary and Secondary Isotope Contributions

2015 ◽  
Vol 119 (30) ◽  
pp. 9532-9546 ◽  
Author(s):  
Prasad Phatak ◽  
Jordan Venderley ◽  
John Debrota ◽  
Junjie Li ◽  
Srinivasan S. Iyengar
Keyword(s):  
Linoleic Acid ◽  
Active Site ◽  
Transfer Rate ◽  
Hydrogen Transfer ◽  
Soybean Lipoxygenase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

scholarly journals Beyond the Active Site: Mechanistic Investigations of the Role of the Secondary Coordination Sphere and Beyond on Multi-Electron Electrocatalytic Reactions and Their Relations Between Kinetics and Thermodynamics

2020 ◽  
Author(s):  
Vincent Wang
Keyword(s):  
Thermodynamic Parameters ◽  
Coordination Sphere ◽  
Active Site ◽  
Rate Constants ◽  
Reduction Reaction ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Secondary Coordination Sphere ◽  
Catalytic Rate ◽  
Rate Limiting

<p>The development of an electrocatalyst with a rapid turnover frequency, low overpotential and long-term stability is highly desired for fuel-forming reactions, such as water splitting and CO<sub>2</sub> reduction. The findings of the scaling relationships between the catalytic rate and thermodynamic parameters over a wide range of electrocatalysts in homogeneous and heterogeneous systems provide useful guidelines and predictions for designing better catalysts for those redox reactions. However, such relationships also suggest that a catalyst with a high catalytic rate is typically associated with a high overpotential for a given reaction. Inspired by enzymes, the introduction of additional interactions through the secondary coordination sphere beyond the active site, such as hydrogen-bonding or electrostatic interactions, have been shown to offer a promising avenue to disrupt these unfavorable relationships. Herein, we further investigate the influence of these cooperative interactions on the faster chemical steps, in addition to the rate-limiting step widely examined before, for molecular electrocatalysts with the structural and electronic modifications designed to facilitate the dioxygen reduction reaction, CO<sub>2</sub> reduction reaction and hydrogen evolving reaction. Based on the electrocatalytic kinetic analysis, the rate constants for faster chemical steps and their correlation with the corresponding thermodynamic parameters are evaluated. The results suggest that the effects of the secondary coordination sphere and beyond on these fuel-forming reactions are not necessarily beneficial for promoting all chemical steps and no apparent relation between rate constants and thermodynamic parameters are found in some cases studied here, which may implicate the design of electrocatalysts in the future. Finally, these analyses demonstrate that the characteristic features for voltammograms and foot-of-the-wave-analysis plots are associated with the specific kinetic phenomenon among these multi-electron electrocatalytic reactions, which provides a useful framework to probe the insights of chemical and electronic modifications on the catalytic steps quantitatively (i.e. kinetic rate constants) and to optimize some of critical steps beyond the rate-limiting step.</p>

scholarly journals Kinetic modelling of hydrogen transfer deoxygenation of a prototypical fatty acid over a bimetallic Pd60Cu40 catalyst: an investigation of the surface reaction mechanism and rate limiting step

2020 ◽  
Vol 5 (9) ◽  
pp. 1682-1693
Author(s):  
Kin Wai Cheah ◽  
Suzana Yusup ◽  
Martin J. Taylor ◽  
Bing Shen How ◽  
Amin Osatiashtiani ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Reaction Mechanism ◽  
Hydrogen Transfer ◽  
Surface Reaction ◽  
Kinetic Modelling ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Cu Catalyst ◽  
P Application ◽  
Rate Limiting

Application of tetralin as a source of hydrogen for catalytic conversion of oleic acid to diesel-like hydrocarbons using a bimetallic Pd–Cu catalyst.

scholarly journals The influence of active site conformations on the hydride transfer step of the thymidylate synthase reaction mechanism

2015 ◽  
Vol 17 (46) ◽  
pp. 30793-30804 ◽  
Author(s):  
Katarzyna Świderek ◽  
Amnon Kohen ◽  
Vicent Moliner
Keyword(s):  
Reaction Mechanism ◽  
Thymidylate Synthase ◽  
Active Site ◽  
Hydride Transfer ◽  
Md Simulations ◽  
Concerted Mechanism ◽  
X Ray ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

QM/MM MD simulations from different X-ray structures support the concerted mechanism character in the rate limiting step of thymidylate synthase catalysis.

Thermal Decomposition of Aromatic Thioureas [1]

1986 ◽  
Vol 41 (1) ◽  
pp. 101-104 ◽  
Author(s):  
Cyril Párkányi ◽  
Mohammed A. Al-Salamah
Keyword(s):  
Thermal Decomposition ◽  
Hydrogen Transfer ◽  
Chemical Reactivity ◽  
Order Reaction ◽  
First Order ◽  
Reactivity Indices ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Intramolecular Hydrogen ◽  
Rate Limiting

Thermal decomposition of aromatic and heteroaromatic thioureas in boiling chlorobenzene is a first-order reaction. The reaction involves intramolecular hydrogen transfer followed by a cleavage of the C - N bond which is the rate-limiting step. The rate constants of decom position have been determined and correlated with quantum-chemical reactivity indices.

scholarly journals Biochemical characterization of a trypanosome enzyme with glutathione-dependent peroxidase activity

2000 ◽  
Vol 352 (3) ◽  
pp. 755-761 ◽  
Author(s):  
Shane R. WILKINSON ◽  
David J. MEYER ◽  
John M. KELLY
Keyword(s):  
Linoleic Acid ◽  
Peroxidase Activity ◽  
Biochemical Characterization ◽  
Linoleic Acid Hydroperoxide ◽  
Butyl Hydroperoxide ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Wide Range ◽  
Acid Hydroperoxide ◽  
Rate Limiting

In most eukaryotes, glutathione-dependent peroxidases play a key role in the metabolism of peroxides. Numerous studies have reported that trypanosomatids lack this activity. Here we show that this is not the case, at least for the American trypanosome Trypanosoma cruzi. We have isolated a single-copy gene from T. cruzi with the potential to encode an 18kDa enzyme, the sequence of which has highest similarity with glutathione peroxidases from plants. A recombinant form of the protein was purified following expression in Escherichia coli. The enzyme was shown to have peroxidase activity in the presence of glutathione/glutathione reductase but not in the presence of trypanothione/trypanothione reductase. It could metabolize a wide range of hydroperoxides (linoleic acid hydroperoxide and phosphatidylcholine hydroperoxide> cumene hydroperoxide>t-butyl hydroperoxide), but no activity towards hydrogen peroxide was detected. Enzyme activity could be saturated by glutathione when both fatty acid and short-chain organic hydroperoxides were used as substrate. For linoleic acid hydroperoxide, the rate-limiting step of this reaction is the reduction of the peroxidase by glutathione. With lower-affinity substrates such as t-butyl hydroperoxide, the rate-limiting step is the reduction of the oxidant. The data presented here identify a new arm of the T. cruzi oxidative defence system.

scholarly journals Beyond the Active Site: Mechanistic Investigations of the Role of the Secondary Coordination Sphere and Beyond on Multi-Electron Electrocatalytic Reactions and Their Relations Between Kinetics and Thermodynamics

2020 ◽  
Author(s):  
Vincent Wang
Keyword(s):  
Thermodynamic Parameters ◽  
Coordination Sphere ◽  
Active Site ◽  
Rate Constants ◽  
Reduction Reaction ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Secondary Coordination Sphere ◽  
Catalytic Rate ◽  
Rate Limiting

<p>The development of an electrocatalyst with a rapid turnover frequency, low overpotential and long-term stability is highly desired for fuel-forming reactions, such as water splitting and CO<sub>2</sub> reduction. The findings of the scaling relationships between the catalytic rate and thermodynamic parameters over a wide range of electrocatalysts in homogeneous and heterogeneous systems provide useful guidelines and predictions for designing better catalysts for those redox reactions. However, such relationships also suggest that a catalyst with a high catalytic rate is typically associated with a high overpotential for a given reaction. Inspired by enzymes, the introduction of additional interactions through the secondary coordination sphere beyond the active site, such as hydrogen-bonding or electrostatic interactions, have been shown to offer a promising avenue to disrupt these unfavorable relationships. Herein, we further investigate the influence of these cooperative interactions on the faster chemical steps, in addition to the rate-limiting step widely examined before, for molecular electrocatalysts with the structural and electronic modifications designed to facilitate the dioxygen reduction reaction, CO<sub>2</sub> reduction reaction and hydrogen evolving reaction. Based on the electrocatalytic kinetic analysis, the rate constants for faster chemical steps and their correlation with the corresponding thermodynamic parameters are evaluated. The results suggest that the effects of the secondary coordination sphere and beyond on these fuel-forming reactions are not necessarily beneficial for promoting all chemical steps and no apparent relation between rate constants and thermodynamic parameters are found in some cases studied here, which may implicate the design of electrocatalysts in the future. Finally, these analyses demonstrate that the characteristic features for voltammograms and foot-of-the-wave-analysis plots are associated with the specific kinetic phenomenon among these multi-electron electrocatalytic reactions, which provides a useful framework to probe the insights of chemical and electronic modifications on the catalytic steps quantitatively (i.e. kinetic rate constants) and to optimize some of critical steps beyond the rate-limiting step.</p>

scholarly journals Structural elucidation of the heterodimeric cis-prenyltransferase NgBR/DHDDS complex reveals novel insights in regulation of protein glycosylation

2020 ◽  
Author(s):  
Ban Edani ◽  
Kariona A. Grabińska ◽  
Rong Zhang ◽  
Eon Joo Park ◽  
Benjamin Siciliano ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Protein Glycosylation ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Chain Synthesis ◽  
Rate Limiting ◽  
Activity Comparison ◽  
Long Chain ◽  
Resolution Structure

SummaryCis-prenyltransferase (cis-PTase) catalyzes the rate-limiting step in the synthesis of glycosyl carrier lipids required for protein glycosylation in the lumen of endoplasmic reticulum. Here we report the crystal structure of the human NgBR/DHDDS complex, which represents the first atomic resolution structure for any heterodimeric cis-PTase. The crystal structure sheds light on how NgBR stabilizes DHDDS through dimerization, participates in the enzyme’s active site through its C-terminal -RXG- motif, and how phospholipids markedly stimulate cis-PTase activity. Comparison of NgBR/DHDDS with homodimeric cis-PTase structures leads to a model where the elongating isoprene chain extends beyond the enzyme’s active site tunnel, and an insert within the α3 helix helps to stabilize this energetically unfavorable state to enable long chain synthesis to occur. These data provide unique insights into how heterodimeric cis-PTases have evolved from their ancestral, homodimeric forms to fulfill their function in long chain polyprenol synthesis.

Studies on the structure and mechanism of H-ras p21

1992 ◽  
Vol 336 (1276) ◽  
pp. 3-11 ◽  
Keyword(s):  
Active Site ◽  
Current Knowledge ◽  
Major Change ◽  
Gtpase Activating Protein ◽  
Gtp Hydrolysis ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Ras P21 ◽  
Loop 2 ◽  
Rate Limiting

Current knowledge of the structure of H-ras p21 is reviewed with particular emphasis on the interaction between guanine nucleotides and the active site of the protein. The nature of the conformational change induced by GTP hydrolysis is discussed. The major change is seen in the region known as the effector loop (loop 2), with significant but less well-defined changes occurring in loop 4, which is implicated in the GTPase reaction. Other evidence concerning the mechanism of GTP hydrolysis and its activation by GAP (GTPase-activating protein) is also discussed. Evidence regarding the rate limiting step in the p21 GTPase reaction, and the manner in which this and possibly other steps are accelerated by GAP, is inconclusive.

scholarly journals Structural elucidation of thecis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation

2020 ◽  
Vol 117 (34) ◽  
pp. 20794-20802 ◽  
Author(s):  
Ban H. Edani ◽  
Kariona A. Grabińska ◽  
Rong Zhang ◽  
Eon Joo Park ◽  
Benjamin Siciliano ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Protein Glycosylation ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Chain Synthesis ◽  
Rate Limiting ◽  
Activity Comparison ◽  
Long Chain ◽  
Resolution Structure

Cis-prenyltransferase (cis-PTase) catalyzes the rate-limiting step in the synthesis of glycosyl carrier lipids required for protein glycosylation in the lumen of endoplasmic reticulum. Here, we report the crystal structure of the human NgBR/DHDDS complex, which represents an atomic resolution structure for any heterodimericcis-PTase. The crystal structure sheds light on how NgBR stabilizes DHDDS through dimerization, participates in the enzyme’s active site through its C-terminal -RXG- motif, and how phospholipids markedly stimulatecis-PTase activity. Comparison of NgBR/DHDDS with homodimericcis-PTase structures leads to a model where the elongating isoprene chain extends beyond the enzyme’s active site tunnel, and an insert within the α3 helix helps to stabilize this energetically unfavorable state to enable long-chain synthesis to occur. These data provide unique insights into how heterodimericcis-PTases have evolved from their ancestral, homodimeric forms to fulfill their function in long-chain polyprenol synthesis.

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