scholarly journals Explaining Urease Specificity Towards Nickel: A Re-Analysis of Its Proposed Mechanism

2020 ◽  
Author(s):  
Millena Pereira Ferreira ◽  
Caio Bezerra de Castro ◽  
Caterina Gruenwaldt Cunha Marques Netto
Keyword(s):  
Catalytic Reaction ◽  
Catalytic Efficiency ◽  
Careful Analysis ◽  
Rate Enhancement ◽  
Nickel Centers

Urease is a binuclear metalloenzyme selective towards nickel, exhibiting a remarkable rate enhancement of the catalytic reaction. The accepted mechanism for urease describes the coordination of urea to both nickel centers in an O,N bridged mode, enabling the attack of the carbonyl by a bridged hydroxide present between the metallic centers. However, the substitution of nickel by other metals significantly reduces urease´s catalytic efficiency. The proposed mechanism cannot explain this difference in activity since it does not follow a rational nucleophilicity scale. After a careful analysis of the literature data on thermodynamics, kinetics, inhibition, and mutations, we verified that by analyzing the mechanism from a diffrent angle, another pathway is most likely occuring. This mechanism can explain urease´s selectivity towards nickel and all the data present in the literature, gathering amost a century of study about urease.

scholarly journals Explaining Urease Specificity Towards Nickel: A Re-Analysis of Its Proposed Mechanism

2020 ◽  
Author(s):  
Millena Pereira Ferreira ◽  
Caio Bezerra de Castro ◽  
Caterina Gruenwaldt Cunha Marques Netto
Keyword(s):  
Catalytic Reaction ◽  
Catalytic Efficiency ◽  
Careful Analysis ◽  
Rate Enhancement ◽  
Nickel Centers

Urease is a binuclear metalloenzyme selective towards nickel, exhibiting a remarkable rate enhancement of the catalytic reaction. The accepted mechanism for urease describes the coordination of urea to both nickel centers in an O,N bridged mode, enabling the attack of the carbonyl by a bridged hydroxide present between the metallic centers. However, the substitution of nickel by other metals significantly reduces urease´s catalytic efficiency. The proposed mechanism cannot explain this difference in activity since it does not follow a rational nucleophilicity scale. After a careful analysis of the literature data on thermodynamics, kinetics, inhibition, and mutations, we verified that by analyzing the mechanism from a diffrent angle, another pathway is most likely occuring. This mechanism can explain urease´s selectivity towards nickel and all the data present in the literature, gathering amost a century of study about urease.

A catalyst for ester hydrolysis showing electrostatic and hydrophobic binding properties

1976 ◽  
Vol 54 (17) ◽  
pp. 2745-2758 ◽  
Author(s):  
J. Peter Guthrie ◽  
Yasutsugu Ueda
Keyword(s):  
Ionic Strength ◽  
Electrostatic Interactions ◽  
Hydrophobic Effect ◽  
Catalytic Efficiency ◽  
Lower Surface ◽  
Imidazole Ring ◽  
Progressive Increase ◽  
Aryl Group ◽  
Rate Enhancement ◽  
Hydrophobic Binding

The steroid 17β-(4-imidazolyl)-5α-androstane-3β,11β-diamine, 1a, R = H, acts as a catalyst for the hydrolysis of aryl esters. For a series of aryl acetates, 2a–h, at 1 M ionic strength, log k2 for 1a catalyzed hydrolysis is linearly related to log k2 for imidazole catalyzed hydrolysis, with only 2d, 4-acetoxy-3-nitrobenzoate, deviating: at zero ionic strength, all anionic substrates show positive deviations, and a cationic substrate shows a negative deviation. This is interpreted in terms of a stringent geometrical requirement for strong electrostatic catalysis. With favorable geometry, a 1:1 electrostatic attraction can lead to a 15 fold rate enhancement (μ = 0). For a series of arylpropionate esters 3a–c, rate constants for 1a catalyzed hydrolysis show a small but progressive increase with increasing size of the aryl group: after correcting for substrate reactivity and electrostatic interactions, this hydrophobic effect is independent of the leaving group. 1b (R = isopropyl) was prepared to determine the rate of reaction at N-3 of the steroidal imidazole ring: this is the more hindered nitrogen but also the more suitable for hydrophobic binding. 1b was markedly less reactive than 1a, but showed larger hydrophobic effects. Detailed analysis suggests that the potential hydrophobic rate enhancement for the interaction of a phenanthryl group with the lower surface of a steroid is about 160-fold. This study provides guidelines for the design of enzyme models of greater catalytic efficiency.

Analysis of Dark-Field Images of Disordered Materials

1972 ◽  
Vol 30 ◽  
pp. 560-561
Author(s):  
J. M. Cowley
Keyword(s):  
Amorphous Materials ◽  
Careful Analysis ◽  
Dark Field ◽  
Minimum Diameter ◽  
Statistical Fluctuations ◽  
Bright Spots ◽  
Sufficient Detail ◽  
Random Arrangement ◽  
Diffraction Patterns ◽  
Imaging Conditions

Recently a number of authors have reported detail in dark-field images obtained from diffuse-scattering regions of electron diffraction patterns. Bright spots in images from short-range order diffuse peaks of disordered binary alloys have been interpreted as evidence for the existence of microdomains of ordered lattice or of segragated clusters of one component. Spotty contrast in dark field images of near-amorphous materials has been interpreted as evidence for the existense of microcrystals. Without a careful analysis of the imaging conditions such conclusions may be invalid. Usually the conditions of the experiment have not been specified in sufficient detail to allow evaluation of the conclusions.Elementary considerations show that even for a completely random arrangement of atoms the statistical fluctuations of density will give a spotty contrast with spots of minimum diameter determined by the dark field aperture size and other factors influencing the minimum resolvable distance under darkfield imaging conditions, including fluctuations and drift over long exposure times (resolution usually 10Å or more).

Left Ventricular Hypertrophy

2014 ◽  
Vol 19 (2) ◽  
pp. 11-15
Author(s):  
Steven L. Demeter
Keyword(s):  
Risk Factors ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Left Ventricular Mass Index ◽  
Medical Science ◽  
Careful Analysis ◽  
Left Ventricular ◽  
Hypertensive Disease ◽  
Accurate Analysis ◽  
Clear Explanation

Abstract The fourth, fifth, and sixth editions of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) use left ventricular hypertrophy (LVH) as a variable to determine impairment caused by hypertensive disease. The issue of LVH, as assessed echocardiographically, is a prime example of medical science being at odds with legal jurisprudence. Some legislatures have allowed any cause of LVH in a hypertensive individual to be an allowed manifestation of hypertensive changes. This situation has arisen because a physician can never say that no component of LVH was not caused by the hypertension, even in an individual with a cardiomyopathy or valvular disorder. This article recommends that evaluators consider three points: if the cause of the LVH is hypertension, is the examinee at maximum medical improvement; is the LVH caused by hypertension or another factor; and, if apportionment is allowed, then a careful analysis of the risk factors for other disorders associated with LVH is necessary. The left ventricular mass index should be present in the echocardiogram report and can guide the interpretation of the alleged LVH; if not present, it should be requested because it facilitates a more accurate analysis. Further, if the cause of the LVH is more likely independent of the hypertension, then careful reasoning and an explanation should be included in the impairment report. If hypertension is only a partial cause, a reasoned analysis and clear explanation of the apportionment are required.

Heparin and Low Molecular Weight Heparins Inhibit Prothrombinase Formation but not its Activity in Plasma

1994 ◽  
Vol 72 (06) ◽  
pp. 862-868 ◽  
Author(s):  
Frederick A Ofosu ◽  
J C Lormeau ◽  
Sharon Craven ◽  
Lori Dewar ◽  
Noorildan Anvari
Keyword(s):  
Factor Xa ◽  
Catalytic Efficiency ◽  
Thrombin Inhibitor ◽  
Lag Phase ◽  
Factor V ◽  
Factor X ◽  
Normal Plasma ◽  
Plasma Factor ◽  
Prothrombin Activation ◽  
Plasma Heparin

SummaryFactor V activation is a critical step preceding prothrombinase formation. This study determined the contributions of factor Xa and thrombin, which activate purified factor V with similar catalytic efficiency, to plasma factor V activation during coagulation. Prothrombin activation began without a lag phase after a suspension of coagulant phospholipids, CaCl2, and factor Xa was added to factor X-depleted plasma. Hirudin, a potent thrombin inhibitor, abrogated prothrombin activation initiated with 0.5 and 1.0 nM factor Xa, but not with 5 nM factor Xa. In contrast, hirudin did not abrogate prothrombin activation in plasmas pre-incubated with 0.5,1.0 or 5 nM α-thrombin for 10 s followed by the coagulant suspension containing 0.5 nM factor Xa. Thus, thrombin activates plasma factor V more efficiently than factor Xa. At concentrations which doubled the clotting time of contact-activated normal plasma, heparin and three low Mr heparins also abrogated prothrombin activation initiated with 0.5 nM factor Xa, but not with 5 nM factor Xa. If factor V in the factor X-depleted plasma was activated (by pre-incubation with 10 nM a-thrombin for 60 s) before adding 0.5,1.0, or 5 nM factor Xa, neither hirudin nor the heparins altered the rates of prothrombin activation. Thus, none of the five anticoagulants inactivates prothrombinase. When 5 or 10 pM relipidated r-human tissue factor and CaCl2 were added to normal plasma, heparin and the three low Mr heparins delayed the onset of prothrombin activation until the concentration of factor Xa generated exceeded 1 nM, and they subsequently inhibited prothrombin activation to the same extent. Thus, hirudin, heparin and low Mr heparins suppress prothrombin activation solely by inhibiting prothrombinase formation.

Lack of Tenderness: The Main Culprit for the Relationship between Husband and Wife in Lady Chatterley’s Lover

2017 ◽  
Keyword(s):  
Careful Analysis ◽  
Physical Distance ◽  
Human Society ◽  
Human Relationships ◽  
Main Culprit ◽  
Industrial Civilization ◽  
Lady Chatterley's Lover ◽  
The Relationship ◽  
Winter Hibernation ◽  
Husband And Wife

This article presents the case of Chatterley and Clifford, the two main characters in Lady Chatterley’s Lover, to consider tenderness a basic working emotion to shape human relationships. The lack of tenderness causes emotional as well as physical distance in relation, especially that of male-female’s relation. The first part of the article reviews tenderness. The second part reviews how tenderness and lack of tenderness affect a male-female relationship in the selected novel, Lady Chatterley’s Lover. On the basis of a careful analysis of Lady Chatterley’s Lover, the present writer tries to prove that the lack of tenderness is the main culprit for the broken relationship between husband and wife: a major one of the relations between man and woman in human society and mutual tenderness elicits people awakening to a new way of living in an exterior world that is uncracking after the long winter hibernation. Lawrence, through a revelation of Connie’s gradual awakening from tenderness, has made his utmost effort to explore possible solutions to harmonious androgyny between men and women so as to revitalize the distorted human nature caused by the industrial civilization. Key words: relationship, husband and wife, tenderness, main culprit, Connie

Le potentiel théâtral chez David Foenkinos. Analyse du roman, du scénario et du film La Délicatesse

2020 ◽  
Vol 65 (2) ◽  
pp. 297-319
Author(s):  
Aluaș Alina
Keyword(s):  
Text Processing ◽  
Careful Analysis ◽  
The Novel ◽  
Work Analysis ◽  
Personal Myth ◽  
The Subject

"The Theatrical Potential in David Foenkinos’ Work. Analysis of the Novel, the Scenario and the Film “La Délicatesse”. Our interest, especially when it comes to the subject of literature, is to show the manner in which the text processing done by the author (script writer/director) brings to light the guidelines of the novelistic text’s semantics, which under careful analysis reveals a kind of personal myth of the novelist. The skewed, syncopated, interrupted writing which disrupts the chronotope serves the needs of the script as well as the director’s selective vision. Unconsciously, the novel seems to follow the structure of the theatrical model. These traits can also be found in the cinematographic structure of the film. Keywords: love, eroticism, delicacy, theatricality, scenario, film. "

Protein Flexibility Catalyzes a Cell Signaling Reaction of the Ras-GAP Complex

2019 ◽  
Author(s):  
Keiei Kumon ◽  
Masahiro Higashi ◽  
Shinji Saito ◽  
Shigehiko Hayashi
Keyword(s):  
Cell Signaling ◽  
Conformational Changes ◽  
Catalytic Reaction ◽  
Protein Complex ◽  
Enzyme Mechanism ◽  
Activation Free Energy ◽  
Chemical Catalysis ◽  
Simple Chemical ◽  
A Cell ◽  
Enzyme Molecules

Many enzyme molecules exhibit characteristic global and slow dynamics which furnish them with allostery realizing remarkable molecular functionalities more than simple chemical catalysis. However, molecular mechanism of a catalytic reaction associated with the molecular flexibility of enzymes is not well-understood. Here we report a hybrid molecular simulation study on GTPase activity of a Ras-GAP protein complex for cell signaling termination. We unveiled that extensive conformational changes of the protein complex and exclusion of internal water molecules are induced upon the transition state (TS) formation in the catalytic reaction and significantly lower the reaction activation free energy. We also revealed that tumor-related mutations perturb those conformational changes upon the TS formation, leading to reduction of the catalytic activity. The findings of the remarkably dynamic protein conformation directly linking to the catalytic reaction have broad implications for understanding of enzyme mechanism and for developments of allosteric drugs and novel catalysts.

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