scholarly journals Aldehyde dehydrogenase. An enzyme with two distinct catalytic activities at a single type of active site

1985 ◽  
Vol 230 (1) ◽  
pp. 261-267 ◽  
Author(s):  
R J Duncan
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Active Site ◽  
Active Sites ◽  
Catalytic Site ◽  
Single Type ◽  
Catalytic Activities ◽  
Binding Domains

The evidence for and against the esterase and dehydrogenase active sites of aldehyde dehydrogenase being topologically distinct is examined. It is found that all the evidence (including all that previously amassed by others in favour of distinct binding domains) is actually consistent with, and in favour of, a single type of catalytic site having both activities. The existence of separate high-Km modulating sites for the enzyme is also questioned.

scholarly journals Inactivation of horse liver mitochondrial aldehyde dehydrogenase by disulfiram. Evidence that disulfiram is not an active-site-directed reagent

1987 ◽  
Vol 242 (2) ◽  
pp. 499-503 ◽  
Author(s):  
C G Sanny ◽  
H Weiner
Keyword(s):  
Catalytic Activity ◽  
Aldehyde Dehydrogenase ◽  
Active Site ◽  
Active Sites ◽  
Specific Activity ◽  
Cysteine Residue ◽  
Complete Inactivation ◽  
Horse Liver ◽  
Inactivation Mechanism ◽  
Liver Aldehyde Dehydrogenase

The inhibition of mitochondrial (pI 5) horse liver aldehyde dehydrogenase by disulfiram (tetraethylthiuram disulphide) was investigated to determine if the drug was an active-site-directed inhibitor. Stoichiometry of inhibition was determined by using an analogue, [35S]tetramethylthiuram disulphide. A 50% loss of the dehydrogenase activity was observed when only one site per tetrameric enzyme was modified, and complete inactivation was not obtained even after seven sites per tetramer were modified. Modification of only two sites accounted for a loss of 75% of the initial catalytic activity. The number of functioning active sites per tetrameric enzyme, as determined by the magnitude of the pre-steady-state burst of NADH formation, did not decrease until approx. 75% of the catalytic activity was lost. These data indicate that disulfiram does not modify the essential nucleophilic amino acid at the active site of the enzyme. The data support an inactivation mechanism involving the formation of a mixed disulphide with a non-essential cysteine residue, resulting in a lowered specific activity of the enzyme.

Dual-Function, Light Switchable Cobalt Catalysis via Active Site Metamorphosis

2019 ◽  
Author(s):  
Enrico Bergamaschi ◽  
Frédéric Beltran ◽  
Christopher Teskey
Keyword(s):  
Visible Light ◽  
Active Site ◽  
Catalytic Site ◽  
Dual Function ◽  
Catalytic Systems ◽  
Hydride Complex ◽  
Dual Functional ◽  
Multiple Processes ◽  
Olefin Migration

<p></p><p></p><p>Switchable catalysis offers opportunities to control the rate or selectivity of a reaction <i>via</i> a stimulus such as pH or light. However, few examples of switchable catalytic systems that can facilitate multiple processes exist. Here we report a rare example of such dual-functional, switchable catalysis. Featuring an easily prepared, bench-stable cobalt(I) hydride complex in conjunction with pinacolborane, we can completely alter the reaction outcome between two widely employed transformations – olefin migration and hydroboration – with visible light as the sole trigger. This dichotomy arises from ligand photodissociation which leads to metamorphosis of the active catalytic site, resulting in divergent mechanistic pathways.</p><p></p><p></p>

Catalytic Resonance Theory: Parallel Reaction Pathway Control

2019 ◽  
Author(s):  
M. Alexander Ardagh ◽  
Manish Shetty ◽  
Anatoliy Kuznetsov ◽  
Qi Zhang ◽  
Phillip Christopher ◽  
...  
Keyword(s):  
Chemical Reactions ◽  
Active Site ◽  
Active Sites ◽  
Reaction Pathway ◽  
Control Strategies ◽  
Oscillation Amplitude ◽  
Catalytic Performance ◽  
Parallel Reaction ◽  
Resonance Theory ◽  
Static Conditions

Catalytic enhancement of chemical reactions via heterogeneous materials occurs through stabilization of transition states at designed active sites, but dramatically greater rate acceleration on that same active site is achieved when the surface intermediates oscillate in binding energy. The applied oscillation amplitude and frequency can accelerate reactions orders of magnitude above the catalytic rates of static systems, provided the active site dynamics are tuned to the natural frequencies of the surface chemistry. In this work, differences in the characteristics of parallel reactions are exploited via selective application of active site dynamics (0 < ΔU < 1.0 eV amplitude, 10<sup>-6</sup> < f < 10<sup>4</sup> Hz frequency) to control the extent of competing reactions occurring on the shared catalytic surface. Simulation of multiple parallel reaction systems with broad range of variation in chemical parameters revealed that parallel chemistries are highly tunable in selectivity between either pure product, even when specific products are not selectively produced under static conditions. Two mechanisms leading to dynamic selectivity control were identified: (i) surface thermodynamic control of one product species under strong binding conditions, or (ii) catalytic resonance of the kinetics of one reaction over the other. These dynamic parallel pathway control strategies applied to a host of chemical conditions indicate significant potential for improving the catalytic performance of many important industrial chemical reactions beyond their existing static performance.

Identification of a Functionally Important Negatively Charged Residue Within the Second Catalytic Site of the SUR1 Nucleotide-Binding Domains

Diabetes ◽  
2004 ◽  
Vol 53 (Supplement 3) ◽  
pp. S123-S127 ◽  
Author(s):  
J. D. Campbell ◽  
P. Proks ◽  
J. D. Lippiat ◽  
M. S.P. Sansom ◽  
F. M. Ashcroft
Keyword(s):  
Nucleotide Binding ◽  
Catalytic Site ◽  
Charged Residue ◽  
Binding Domains

Nonlinear Vibrations in a 2-Dimensional Protein Cluster Model with Linear Bonds

2000 ◽  
Vol 214 (1) ◽  
Author(s):  
E.G. Shidlovskaya ◽  
L. Schimansky-Geier ◽  
Yu.M. Romanovsky
Keyword(s):  
Active Site ◽  
Internal Resonance ◽  
Cluster Model ◽  
Active Sites ◽  
Nonlinear Vibrations ◽  
Nonlinear Phenomena ◽  
Two Dimensional ◽  
Dimensional Model ◽  
Two Dimensional Model

A two dimensional model for the substrate inside a pocket of an active site of an enzyme is presented and investigated as a vibrational system. The parameters of the system are evaluated for α-chymotrypsin. In the case of internal resonance it is analytically and numerically shown that the energy concentrated on a certain degree of freedom might be several times larger than in the non-resonant case. Additionally, the system is driven by harmonic excitations and again energy due to nonlinear phenomena is redistributed inhomogeneously. These results may be of importance for the determination of the rates of catalytic events of substrates bound in pockets of active sites.

Effect of Modifiers on the Hydrolysis of Basic and Neutral Peptides by Carboxypeptidase B

1975 ◽  
Vol 53 (7) ◽  
pp. 747-757 ◽  
Author(s):  
Graham J. Moore ◽  
N. Leo Benoiton
Keyword(s):  
Active Site ◽  
Active Sites ◽  
Kinetic Behavior ◽  
Carboxypeptidase A ◽  
Phenyllactic Acid ◽  
Carboxypeptidase B ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
Basic Peptides ◽  
Hydrolysis Of

The initial rates of hydrolysis of Bz-Gly-Lys and Bz-Gly-Phe by carboxypeptidase B (CPB) are increased in the presence of the modifiers β-phenylpropionic acid, cyclohexanol, Bz-Gly, and Bz-Gly-Gly. The hydrolysis of the tripeptide Bz-Gly-Gly-Phe is also activated by Bz-Gly and Bz-Gly-Gly, but none of these modifiers activate the hydrolysis of Bz-Gly-Gly-Lys, Z-Leu-Ala-Phe, or Bz-Gly-phenyllactic acid by CPB. All modifiers except cyclohexanol display inhibitory modes of binding when present in high concentration.Examination of Lineweaver–Burk plots in the presence of fixed concentrations of Bz-Gly has shown that activation of the hydrolysis of neutral and basic peptides by CPB, as reflected in the values of the extrapolated parameters, Km(app) and keat, occurs by different mechanisms. For Bz-Gly-Gly-Phe, activation occurs because the enzyme–modifier complex has a higher affinity than the free enzyme for the substrate, whereas activation of the hydrolysis of Bz-Gly-Lys derives from an increase in the rate of breakdown of the enzyme–substrate complex to give products.Cyclohexanol differs from Bz-Gly and Bz-Gly-Gly in that it displays no inhibitory mode of binding with any of the substrates examined, activates only the hydrolysis of dipeptides by CPB, and has a greater effect on the hydrolysis of the basic dipeptide than on the neutral dipeptide. Moreover, when Bz-Gly-Lys is the substrate, cyclohexanol activates its hydrolysis by CPB by increasing both the enzyme–substrate binding affinity and the rate of the catalytic step, an effect different from that observed when Bz-Gly is the modifier.The anomalous kinetic behavior of CPB is remarkably similar to that of carboxypeptidase A, and is a good indication that both enzymes have very similar structures in and around their respective active sites. A binding site for activator molecules down the cleft of the active site is proposed for CPB to explain the observed kinetic behavior.

scholarly journals Photolabelling of Salmonella typhimurium LT2 sialidase. Identification of a peptide with a predicted structural similarity to the active sites of influenza-virus sialidases

1992 ◽  
Vol 285 (3) ◽  
pp. 957-964 ◽  
Author(s):  
T G Warner ◽  
R Harris ◽  
R McDowell ◽  
E R Vimr
Keyword(s):  
Salmonella Typhimurium ◽  
Active Site ◽  
Influenza A ◽  
Active Sites ◽  
Enzyme Inhibitors ◽  
Structural Similarity ◽  
Competitive Inhibitor ◽  
Beta Sheets ◽  
Sialidase Inhibitor ◽  
Active Site Cavity

The sialidase from Salmonella typhimurium LT2 was characterized by using photoaffinity-labelling techniques. The well-known sialidase inhibitor 5-acetamido-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non- 2-enonic acid (Neu5Ac2en) was modified to contain an amino group at C-9, which permitted the incorporation of 4-azidosalicylic acid in amide linkage at this position. Labelling of the purified protein with the radioactive (125I) photoprobe was determined to be highly specific for a region within the active-site cavity. This conclusion was based on the observation that the competitive inhibitor Neu5Ac2en in the photolysis mixture prevented labelling of the protein. In contrast, compounds with structural and chemical features similar to the probe and Neu5Ac2en, but which were not competitive enzyme inhibitors, did not affect the photolabelling of the protein. The peptide interacting with the probe was identified by CNBr treatment of the labelled protein, followed by N-terminal sequence analysis. Inspection of the primary structure of the protein, predicted from the cloned structural gene for the sialidase [Hoyer, Hamilton, Steenbergen & Vimr (1992) Mol. Microbiol. 6, 873-884] revealed that the label was incorporated into a 9.6 kDa fragment situated within the terminal third of the molecule near the C-terminal end. Secondary-structural predictions using the Garnier-Robson algorithm [Garnier, Osguthorpe & Robson (1978) J. Mol. Biol. 120, 97-120] of the labelled peptide revealed a structural similarity to the active site of influenza-A- and Sendai-HN-virus sialidases with a repetitive series of alternating beta-sheets connected with loops.

scholarly journals Multiplicity of Active-Site in Heterogeneous Ziegler-Natta Catalyst and Its Correlation with Polymer Microstructure

1970 ◽  
Vol 46 (4) ◽  
pp. 487-494
Author(s):  
ATM Kamrul Hasan
Keyword(s):  
Molecular Weight ◽  
Computer Simulation ◽  
Active Site ◽  
Photoelectron Spectroscopy ◽  
Active Sites ◽  
Chain Structure ◽  
Surface Complexes ◽  
Polymer Microstructure ◽  
Natta Catalyst ◽  
Ziegler Natta Catalyst

Multiplicity of active-site in heterogeneous Ziegler-Natta catalysts and its correlation with polymer microstructure was studied through the surface structure analysis of catalyst by computer simulation of X-ray Photoelectron Spectroscopy (XPS) data and microstructure investigation of polypropylene chains based on the deconvolution of the molecular weight distribution curves by multiple Flory most probable distributions using Gel Permeation Chromatography (GPC) method. The number and relative intensities of these peaks were found correlated to the distribution of multiple active sites. In this investigation, four individual categories of active sites were identified, each of which yields polypropylene with unique properties of molecular weight and chain structure different from other active sites. The reason of the multiplicity of active sites was determined by the presence of different locations of surface titanium species coordinated with other surface atoms or molecules. These different surface complexes of active species determine the multiple active site nature of catalyst which replicates the microtacticity, molecular weight and chain microstructure distribution of polymer. Keywords: Ziegler-Natta catalyst; Multiple active sites; Flory components; Computer simulation; Deconvolution; MWD. DOI: http://dx.doi.org/10.3329/bjsir.v46i4.9596 BJSIR 2011; 46(4): 487-494

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