Interrogating l-fuconate dehydratase with tartronate and 3-hydroxypyruvate reveals subtle differences within the mandelate racemase-subgroup of the enolase superfamily.

Enzymes of the enolase superfamily share a conserved structure and a common partial reaction (i.e., metal-assisted, Brønsted base-catalyzed enol(ate) formation).

A novel quinoline-appended chalcone derivative as potential gametocytocide.

Background & Objectives: Malaria has remained a global health problem despite the effective control and treatment measures. In the backdrop of drug resistance, developing novel hybrid molecules targeting the sexual stages (gametocytes) of the human malaria parasite Plasmodium falciparum is of great significance. Recently, chalcone- based polyphenols have generated a great interest in the malaria research community worldwide due to their ease of synthesis and significant biological activity.

A Chalcone-Based Potential Therapeutic Small Molecule That Binds to Subdomain IIA in HSA Precisely Controls the Rotamerization of Trp-214.

The principal intent of this work is to explore whether the site-specific binding of a newly synthesized quinoline-appended anthracenyl chalcone, ()-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ), with an extracellular protein of the human circulatory system, human serum albumin (HSA), can control the rotamerization of its sole tryptophan residue, Trp-214. With this aim, we have systematically studied the binding affinity, interactions, and localization pattern of the title compound inside the specific binding domain of the transport protein and any conformation alteration caused therein. Multiple spectroscopic experiments substantiated by an in silico molecular modeling exercise provide evidence for the binding of the guest ADMQ in the hydrophobic domain of HSA, which is primarily constituted by residues Trp-214, Arg-218, Arg-222, Asp-451, and Tyr-452.

Changes in quaternary structure cause a kinetic asymmetry of glutamate racemase-catalyzed homocysteic acid racemization.

Glutamate racemases (GR) catalyze the racemization of d- and l-glutamate and are targets for the development of antibiotics. We demonstrate that GR from the periodontal pathogen Fusobacterium nucleatum (FnGR) catalyzes the racemization of d-homocysteic acid (d-HCA), while l-HCA is a poor substrate. This enantioselectivity arises because l-HCA perturbs FnGR's monomer-dimer equilibrium toward inactive monomer.

A platform for chemical modification of mandelate racemase: characterization of the C92S/C264S and γ-thialysine 166 variants.

Mandelate racemase (MR) serves as a paradigm for our understanding of enzyme-catalyzed deprotonation of a carbon acid substrate. To facilitate structure-function studies on MR using non-natural amino acid substitutions, we engineered the Cys92Ser/Cys264Ser variant (dmMR) as a platform for introducing Cys residues at specific locations for subsequent covalent modification. While the highly reactive thiol of Cys furnishes a site for chemical modification, site-specificity requires that other Cys residues be non-reactive or replaced by a non-reactive amino acid, especially if chemical modification is conducted under denaturing conditions.

Is the Sudlow site I of human serum albumin more generous to adopt prospective anti-cancer bioorganic compound than that of bovine: A combined spectroscopic and docking simulation approach.

A comparative biophysical study on the individual conformational adaptation embraced by two homologous serum albumins (SA) (bovine and human) towards a potential anticancer bioorganic compound 2-(6-chlorobenzo[d] thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)- dione (CBIQD) is apparent from the discrimination in binding behavior and the ensuing consequences accomplished by combined in vitro optical spectroscopy, in silico molecular docking and molecular dynamics (MD) simulation. The Sudlow site I of HSA although anion receptive, harbors neutral CBIQD in Sudlow site I (subdomain IIA, close to Trp) of HSA, while in BSA its prefers to snugly fit into Sudlow site II (subdomain IIIA, close to Tyr). Based on discernable diminution of HSA mean fluorescence lifetime as a function of biluminophore concentration, facile occurrence of fluorescence resonance energy transfer (FRET) is substantiated as the probable quenching mechanism accompanied by structural deformations in the protein ensemble.

Development of multifunctional heterocyclic Schiff base as a potential metal chelator: a comprehensive spectroscopic approach towards drug discovery.

Amyloid-β peptides and their metal-associated aggregated states have been implicated in the pathogenesis of Alzheimer's disease. The present paper epitomises the design and synthesis of a small, neutral, lipophilic benzothiazole Schiff base (E)-2-((6-chlorobenzo[d]thiazol-2-ylimino)methyl)-5-diethylamino)phenol (CBMDP), and explores its multifunctionalty as a potential metal chelator/fluorophore using UV-visible absorption, steady-state fluorescence, single molecule fluorescence correlation spectroscopic (FCS) techniques which is further corroborated by in silico studies. Some pharmaceutically relevant properties of the synthesized compound have also been calculated theoretically.

Conformation controlled turn on-turn off phosphorescence in a metal-free biluminophore: thriving the paradox that exists for organic compounds.

The legacy of phosphorescence from expensive organometallic compounds has inspired researchers to develop efficient metal-free organic phosphors. Although organic phosphors offer a cheaper alternative, the long-lived triplets of organic phosphors that are primarily consumed by vibrational dissipation need to be adequately suppressed, and this provides an opportunity to design new organic entities, at par with the organometallic compounds, based on conformational control and incorporation of useful functional groups to alter their emissive properties, especially phosphorescence. Here, we have achieved a proficient dual state emission, underlining the key design rule of conformational control in an organic molecular platform for 2-(6-chlorobenzo[d]thiazol-2-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (CBIQD).

Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective.

The present study embodies design, in silico DNA interaction, synthesis of benzothiazole containing naphthalimide derivative, 2-(6-chlorobenzo[d]thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)-dione (CBIQD) along with its systematic photophysics, solvatochromic behavior, and solvation dynamics using an experimental and theoretical spectroscopic approach. Steady-state dual emission and biexponential fluorescence decay reveals the formation of two different excited species. Ground- and excited-state optimized geometry and the potential-energy curve obtained from DFT and TD-DFT calculation ascertained the existence of nonplanar and planar conformation.

Design, synthesis, physicochemical studies, solvation, and DNA damage of quinoline-appended chalcone derivative: comprehensive spectroscopic approach toward drug discovery.

The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state.