Valence tautomerism in catecholato cobalt Bis(phenolate) diamine complexes as models for Enzyme–substrate adducts of catechol dioxygenases

We have collected 86 different transforms of tautomeric interconversions. Out of those, 54 are for prototropic (non-ring-chain) tautomerism; 21 for ring-chain tautomerism; and 11 for valence tautomerism. The majority of these rules have been extracted from experimental literature. Twenty rules – covering the most well-known types of tautomerism such as keto-enol tautomerism – were taken from the default handling of tautomerism by the chemoinformatics toolkit CACTVS. The rules were analyzed against nine differerent databases totaling over 400 million (non-unique) structures as to their occurrence rates, mutual overlap in coverage, and recapitulation of the rules’ enumerated tautomer sets by InChI V.1.05, both in InChI’s Standard and a Non-Standard version with the increased tautomer-handling options 15T and KET turned on. These results and the background of this study are discussed in the context of the IUPAC InChI Project tasked with the redesign of handling of tautomerism for an InChI version 2. Applying the rules presented in this paper would approximately triple the number of compounds in typical small-molecule databases that would be affected by tautomeric interconversion by InChI V2. A web tool has been created to test these rules at https://cactus.nci.nih.gov/tautomerizer.

Download Full-text

Cell-Specific Chemical Delivery Using a Selective Nitroreductase–Nitroaryl Pair

10.26434/chemrxiv.6447683.v1 ◽

2018 ◽

Author(s):

Todd D. Gruber ◽

Chithra Krishnamurthy ◽

Jonathan B. Grimm ◽

Michael R. Tadross ◽

Laura M. Wysocki ◽

...

Keyword(s):

Small Molecules ◽

Mammalian Cells ◽

Target Cells ◽

Specific Chemical ◽

E Coli ◽

Enzyme Substrate ◽

Cell Specificity ◽

General Chemical ◽

Increased Activity ◽

Enzyme Variant

The utility of small molecules to probe or perturb biological systems is limited by the lack of cell-specificity. ‘Masking’ the activity of small molecules using a general chemical modification and ‘unmasking’ it only within target cells could overcome this limitation. To this end, we have developed a selective enzyme–substrate pair consisting of engineered variants of E. coli nitroreductase (NTR) and a 2‑nitro-N-methylimidazolyl (NM) masking group. To discover and optimize this NTR–NM system, we synthesized a series of fluorogenic substrates containing different nitroaromatic masking groups, confirmed their stability in cells, and identified the best substrate for NTR. We then engineered the enzyme for improved activity in mammalian cells, ultimately yielding an enzyme variant (enhanced NTR, or eNTR) that possesses up to 100-fold increased activity over wild-type NTR. These improved NTR enzymes combined with the optimal NM masking group enable rapid, selective unmasking of dyes, indicators, and drugs to genetically defined populations of cells.

Download Full-text

Faculty Opinions recommendation of Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1060705.537867 ◽

2007 ◽

Author(s):

Karen Allen

Keyword(s):

Live Cell Imaging ◽

Cell Imaging ◽

Live Cell ◽

Spatial Regulation ◽

Substrate Interaction ◽

Enzyme Substrate

Download Full-text

The role of secondary alcoholic groups of D-galacturonan in its degradation with exo-D-galacturonanase

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19800427 ◽

1980 ◽

Vol 45 (2) ◽

pp. 427-434 ◽

Cited By ~ 4

Author(s):

Kveta Heinrichová ◽

Rudolf Kohn

Keyword(s):

Acetyl Derivative ◽

Competitive Inhibitor ◽

Hydroxyl Groups ◽

Pectic Acid ◽

Substrate Complex ◽

Enzyme Substrate ◽

The Individual ◽

Degradation Degree ◽

Derivatives Of

The effect of exo-D-galacturonanase from carrot on O-acetyl derivatives of pectic acid of variousacetylation degree was studied. Substitution of hydroxyl groups at C(2) and C(3) of D-galactopyranuronic acid units influences the initial rate of degradation, degree of degradation and its maximum rate, the differences being found also in the time of limit degradations of the individual O-acetyl derivatives. Value of the apparent Michaelis constant increases with increase of substitution and value of Vmax changes. O-Acetyl derivatives act as a competitive inhibitor of degradation of D-galacturonan. The extent of the inhibition effect depends on the degree of substitution. The only product of enzymic reaction is D-galactopyranuronic acid, what indicates that no degradation of the terminal substituted unit of O-acetyl derivative of pectic acid takes place. Substitution of hydroxyl groups influences the affinity of the enzyme towards the modified substrate. The results let us presume that hydroxyl groups at C(2) and C(3) of galacturonic unit of pectic acid are essential for formation of the enzyme-substrate complex.

Download Full-text

Mass transfer in heterogeneous system enzyme-substrate; Approximate analytical model for the case of liquid substrate-immobilized enzyme

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19823013 ◽

1982 ◽

Vol 47 (11) ◽

pp. 3013-3018

Author(s):

František Kaštánek ◽

Jindřich Zahradník ◽

Germanico Ocampo

Keyword(s):

Mass Transfer ◽

Heterogeneous System ◽

Immobilized Enzyme ◽

Enzymatic Reaction ◽

Analytical Form ◽

Approximate Model ◽

Basic Type ◽

Reaction Interface ◽

Enzyme Substrate ◽

Flow Intensity

Calculation procedure is suggested for flow intensity of substrate toward reaction interface of immobilized enzyme at simultaneous effect of enzymatic reaction and internal diffusion. The approximate model is presented in an analytical form for the basic type of Michaelis-Menten kinetics and for the case of inhibition in excess of substrate.

Download Full-text