scholarly journals The catalase–hydrogen peroxide system. A theoretical appraisal of the mechanism of catalase action

1968 ◽  
Vol 110 (4) ◽  
pp. 621-629 ◽  
Author(s):  
Peter Jones ◽  
A. Suggett
Keyword(s):  
Active Site ◽  
Molecular Level ◽  
Molecular Model ◽  
Experimental Information ◽  
Theoretical Studies ◽  
Reactive Intermediate ◽  
Acid Base ◽  
System A ◽  
Formal Mechanism ◽  
Base Functions

1. The mechanisms of catalase action advanced by Jones & Wynne-Jones (1962) and by Nicholls (1964) are compared in terms of their relative plausibilities and their utility for extension to accommodate more recent experimental information. 2. A revised formal mechanism is advanced that avoids the less satisfactory features of these mechanisms and attempts to account for the roles of catalase sub-units in both reversible and irreversible deactivation phenomena. 3. Theoretical studies of the redox chemistry of peroxides are used to provide the basis for a discussion of the mechanism of the redox act in catalatic action at the molecular level. It is suggested that an important feature of catalase action may be a mediation of the formation of a reactive intermediate by stereospecifically located acid–base functions in the active site. 4. A more detailed statement of this concept is attempted in terms of a hypothetical partial molecular model for the composition and stereochemistry of the active site of catalase. The utility of this model in describing the catalatic and peroxidatic actions of catalase is assessed.

Theoretical Studies of the Acid–Base Equilibria in a Model Active Site of the Human 20S Proteasome

2021 ◽  
Vol 61 (4) ◽  
pp. 1942-1953
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
20S Proteasome ◽  
Theoretical Studies ◽  
Acid Base

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

2020 ◽  
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
Boronic Acid ◽  
Computational Study ◽  
Ubiquitin Proteasome System ◽  
Bayesian Optimization ◽  
Inhibition Mechanism ◽  
20S Proteasome ◽  
Acid Base ◽  
Ubiquitin Proteasome ◽  
Infection Cycles

The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

scholarly journals Novel hydrogen chemisorption properties of amorphous ceramic compounds consisting of p-block elements: exploring Lewis acid-base Al–N pair site formed in-situ within polymer-derived silicon-aluminum-nitrogen-based system

2021 ◽  
Author(s):  
Shotaro Tada ◽  
Norifumi Asakuma ◽  
Shiori Ando ◽  
Toru Asaka ◽  
Yusuke Daiko ◽  
...  
Keyword(s):  
Lewis Acid ◽  
Active Site ◽  
Hydrogen Chemisorption ◽  
Acid Base ◽  
Polymer Derived Ceramics ◽  
System P ◽  
Ceramic Compounds ◽  
The Relationship

This paper reports on the relationship between the H2 chemisorption properties and reversible structural reorientation of the possible active site around Al formed in-situ within polymer-derived ceramics (PDCs) based on...

Theoretical studies on the magnetic interaction and reversible dioxygen binding of the active site in hemocyanin

2001 ◽  
Vol 335 (5-6) ◽  
pp. 395-403 ◽  
Author(s):  
Yu Takano ◽  
Shigehiro Kubo ◽  
Taku Onishi ◽  
Hiroshi Isobe ◽  
Yasunori Yoshioka ◽  
...  
Keyword(s):  
Active Site ◽  
Magnetic Interaction ◽  
Theoretical Studies

Kinetic characterization of human thyroperoxidase. Normal and pathological enzyme expression in Baculovirus System: A molecular model of functional expression

2015 ◽  
Vol 404 ◽  
pp. 9-15 ◽  
Author(s):  
Fiorella S. Belforte ◽  
Alexandra M. Targovnik ◽  
Rodolfo M. González-Lebrero ◽  
Carolina Osorio Larroche ◽  
Cintia E. Citterio ◽  
...  
Keyword(s):  
Molecular Model ◽  
Functional Expression ◽  
Kinetic Characterization ◽  
Enzyme Expression ◽  
System A ◽  
Baculovirus System

Experimental and Theoretical Studies of Acid−Base Equilibria of Substituted 4-NitropyridineN-Oxides

2003 ◽  
Vol 107 (32) ◽  
pp. 6293-6300 ◽  
Author(s):  
Joanna Berdys ◽  
Mariusz Makowski ◽  
Monika Makowska ◽  
Aniela Puszko ◽  
Lech Chmurzyński
Keyword(s):  
Theoretical Studies ◽  
Acid Base ◽  
Experimental And Theoretical Studies

scholarly journals Molecular mechanism of uncompetitive inhibition of human placental and germ-cell alkaline phosphatase

1992 ◽  
Vol 286 (1) ◽  
pp. 23-30 ◽  
Author(s):  
M F Hoylaerts ◽  
T Manes ◽  
J L Millán
Keyword(s):  
Germ Cell ◽  
Active Site ◽  
Molecular Model ◽  
Inhibition Mechanism ◽  
Side Group ◽  
Alkaline Phosphatases ◽  
Uncompetitive Inhibition ◽  
Guanidinium Group ◽  
Hydrolysis Of ◽  
Site Binding

Placental (PLAP) and germ-cell (GCAP) alkaline phosphatases are inhibited uncompetitively by L-Leu and L-Phe. Whereas L-Phe inhibits PLAP and GCAP to the same extent, L-Leu inhibits GCAP 17-fold more strongly than it does PLAP. This difference has been attributed [Hummer & Millán (1991) Biochem. J 274, 91-95] to a Glu----Gly substitution at position 429 in GCAP. The D-Phe and D-Leu enantiomorphs are also inhibitory through an uncompetitive mechanism but with greatly decreased efficiencies. Replacement of the active-site residue Arg-166 by Ala-166 changes the inhibition mechanism of the resulting PLAP mutant to a more complex mixed-type inhibition, with decreased affinities for L-Leu and L-Phe. The uncompetitive mechanism is restored on the simultaneous introduction of Gly-429 in the Ala-166 mutant, but the inhibitions of [Ala166,Gly429]PLAP and even [Lys166,Gly429]PLAP by L-Leu and L-Phe are considerably decreased compared with that of [Gly429]PLAP. These findings point to the importance of Arg-166 during inhibition. Active-site binding of L-Leu requires the presence of covalently bound phosphate in the active-site pocket, and the inhibition of PLAP by L-Leu is pH-sensitive, gradually disappearing when the pH is decreased from 10.5 to 7.5. Our data are compatible with the following molecular model for the uncompetitive inhibition of PLAP and GCAP by L-Phe and L-Leu: after binding of a phosphorylated substrate to the active site, the guanidinium group of Arg-166 (normally involved in positioning phosphate) is redirected to the carboxy group of L-Leu (or L-Phe), thus stabilizing the inhibitor in the active site. Therefore leucinamide and leucinol are weaker inhibitors of [Gly429]PLAP than is L-Leu. During this Arg-166-regulated event, the amino acid side group is positioned in the loop containing Glu-429 or Gly-429, leading to further stabilization. Replacement of Glu-429 by Gly-429 eliminates steric constraints experienced by the bulky L-Leu side group during its positioning and also increases the active-site accessibility for the inhibitor, providing the basis for the 17-fold difference in inhibition efficiency between PLAP and GCAP. Finally, the inhibitor's unprotonated amino group co-ordinates with the active-site Zn2+ ion 1, interfering with the hydrolysis of the phosphoenzyme intermediate, a phenomenon that determines the uncompetitive nature of the inhibition.

scholarly journals Understanding the Catalytic Activity of Microporous and Mesoporous Zeolites in Cracking by Experiments and Simulations

Catalysts ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1114
Author(s):  
Shih-Cheng Li ◽  
Yen-Chun Lin ◽  
Yi-Pei Li
Keyword(s):  
Catalytic Activity ◽  
Active Site ◽  
Petrochemical Industry ◽  
Molecular Level ◽  
Shape Selectivity ◽  
Zeolite Catalysts ◽  
Hydrocarbon Cracking ◽  
Mesoporous Zeolites ◽  
Secondary Reactions ◽  
Pros And Cons

Porous zeolite catalysts have been widely used in the industry for the conversion of fuel-range molecules for decades. They have the advantages of higher surface area, better hydrothermal stability, and superior shape selectivity, which make them ideal catalysts for hydrocarbon cracking in the petrochemical industry. However, the catalytic activity and selectivity of zeolites for hydrocarbon cracking are significantly affected by the zeolite topology and composition. The aim of this review is to survey recent investigations on hydrocarbon cracking and secondary reactions in micro- and mesoporous zeolites, with the emphasis on the studies of the effects of different porous environments and active site structures on alkane adsorption and activation at the molecular level. The pros and cons of different computational methods used for zeolite simulations are also discussed in this review.

Bicarbonate-carbon dioxide buffer system: a determinant of the mitochondrial pH gradient

1984 ◽  
Vol 247 (3) ◽  
pp. F440-F446 ◽  
Author(s):  
D. P. Simpson ◽  
S. R. Hager
Keyword(s):  
Carbon Dioxide ◽  
Renal Cortex ◽  
Ph Gradient ◽  
Buffer System ◽  
Acid Base ◽  
Bicarbonate Buffer ◽  
Inner Membrane ◽  
System A ◽  
Intact Kidney ◽  
The Difference

The influence of the bicarbonate-carbon dioxide buffer system on the pH gradient (delta pH) across the inner membrane of mitochondria from rabbit renal cortex was studied with and without phosphate in the medium. delta pH with bicarbonate buffer or phosphate in the medium was greater at low than at high medium pH so that the difference (delta delta pH) between delta pH at pH 7.1 and at 7.6 was positive. Varying the concentration of phosphate from 0 to 10 mM had little effect on delta delta pH produced by bicarbonate buffer. Inhibition of the phosphate-hydroxyl carrier with N-ethylmaleimide abolished delta delta pH when phosphate was present in non-bicarbonate-containing media. With bicarbonate buffer present, N-ethylmaleimide increased delta delta pH. Similar effects were observed in mitochondria from liver and heart as well as from kidney. The effects of the bicarbonate buffer system on delta pH may result either from an inner membrane permeable to carbon dioxide but not to bicarbonate ion or from an active carrier for bicarbonate ion in the inner membrane. In intact kidney cells, the influence of the bicarbonate buffer system on delta pH may provide a mechanism for regulating substrate metabolism in response to acid-base changes. It may also serve in many organs to reduce fluctuations in matrix pH when alterations in cytoplasmic pH occur.

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