ternary complex
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Inorganics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 12
Author(s):  
Matteo Savastano ◽  
Valeria Monini ◽  
Carla Bazzicalupi ◽  
Antonio Bianchi

Iodine-dense polyiodide phases are interesting materials for a number of potential uses, including batteries and solid-state conductors. The incorporation of transition metal cations is considered a promising way to enhance the stability, tune the properties, and influence the architecture of polyiodides. However, several interesting metals, including Cu(II), may suffer redox processes, which generally make them not compatible with the I2/I− redox couple. Herein L, a simple derivative of cyclen, is proposed as a Cu(II) ligand capable of protecting the +2 oxidation state of the metal even in the presence of polyiodides. With a step by step approach, we report the crystal structure of free L; then we present spectrophotometric verification of Cu(II) complex stability, stoichiometry, and formation kinetic in DMF solution, together with Cu(II) binding mode elucidation via XRD analysis of [Cu(L)Cl]ClO4∙CH3CN crystals; afterwards, the stability of the CuL complex in the presence of I− is demonstrated in DMF solution, where the formation of a Cu:L:I− ternary complex, rather than reduction to Cu(I), is observed; lastly, polyiodide crystals are prepared, affording the [Cu(L)I]2I3I5 crystal structure. This layered structure is highly peculiar due to its chiral arrangement, opening further perspective for the crystal engineering of polyiodide phases.


Author(s):  
Dhanushka Weerakoon ◽  
Rodrigo J. Carbajo ◽  
Leonardo De Maria ◽  
Christian Tyrchan ◽  
Hongtao Zhao

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Wataru Saburi ◽  
Takanori Nihira ◽  
Hiroyuki Nakai ◽  
Motomitsu Kitaoka ◽  
Haruhide Mori

AbstractGlycoside phosphorylases (GPs), which catalyze the reversible phosphorolysis of glycosides, are promising enzymes for the efficient production of glycosides. Various GPs with new catalytic activities are discovered from uncharacterized proteins phylogenetically distant from known enzymes in the past decade. In this study, we characterized Paenibacillus borealis PBOR_28850 protein, belonging to glycoside hydrolase family 94. Screening of acceptor substrates for reverse phosphorolysis, in which α-d-glucose 1-phosphate was used as the donor substrate, revealed that the recombinant PBOR_28850 produced in Escherichia coli specifically utilized d-galactose as an acceptor and produced solabiose (β-d-Glcp-(1 → 3)-d-Gal). This indicates that PBOR_28850 is a new GP, solabiose phosphorylase. PBOR_28850 catalyzed the phosphorolysis and synthesis of solabiose through a sequential bi-bi mechanism involving the formation of a ternary complex. The production of solabiose from lactose and sucrose has been established. Lactose was hydrolyzed to d-galactose and d-glucose by β-galactosidase. Phosphorolysis of sucrose and synthesis of solabiose were then coupled by adding sucrose, sucrose phosphorylase, and PBOR_28850 to the reaction mixture. Using 210 mmol lactose and 280 mmol sucrose, 207 mmol of solabiose was produced. Yeast treatment degraded the remaining monosaccharides and sucrose without reducing solabiose. Solabiose with a purity of 93.7% was obtained without any chromatographic procedures.


Author(s):  
Kinga Wzgarda-Raj ◽  
Agnieszka J. Rybarczyk-Pirek ◽  
Sławomir Wojtulewski ◽  
Marcin Palusiak

The structures of novel cocrystals of 4-nitropyridine N-oxide with benzenesulfonamide derivatives, namely, 4-nitrobenzenesulfonamide–4-nitropyridine N-oxide (1/1), C5H4N2O3·C6H6N2O4S, and 4-chlorobenzenesulfonamide–4-nitropyridine N-oxide (1/1), C6H6ClNO2S·C5H4N2O3, are stabilized by N—H...O hydrogen bonds, with the sulfonamide group acting as a proton donor. The O atoms of the N-oxide and nitro groups are acceptors in these interactions. The latter is a double acceptor of bifurcated hydrogen bonds. Previous studies on similar crystal structures indicated competition between these functional groups in the formation of hydrogen bonds, with the priority being for the N-oxide group. In contrast, the present X-ray studies indicate the existence of a hydrogen-bonding synthon including N—H...O(N-oxide) and N—H...O(nitro) bridges. We present here a more detailed analysis of the N-oxide–sulfonamide–nitro N—H...O ternary complex with quantum theory computations and the Quantum Theory of Atoms in Molecules (QTAIM) approach. Both interactions are present in the crystals, but the O atom of the N-oxide group is found to be a more effective proton acceptor in hydrogen bonds, with an interaction energy about twice that of the nitro-group O atoms.


2021 ◽  
Author(s):  
Qaiser Waheed ◽  
Huimin Zhou ◽  
Peter Ruoff

Homeostasis plays a central role in our understanding how cells and organisms are able to oppose environmental disturbances and thereby maintain an internal stability. During the last two decades there has been an increased interest in using control engineering methods, especially integral control, in the analysis and design of homeostatic networks. Several reaction kinetic mechanisms have been discovered which lead to integral control. In two of them integral control is achieved, either by the removal of a single control species E by zero-order  kinetics ("single-E controllers"), or by the removal of two control species  by second-order kinetics ("antithetic or dual-E control"). In this paper we show results when the control species E 1  and E 2  in antithetic control are removed enzymatically by ping-pong or ternary-complex mechanisms. Our findings show that enzyme-catalyzed dual-E controllers can work in two control modes. In one mode, one of the two control species is active, but requires zero-order kinetics in its removal. In the other mode, both controller species are active and both are removed enzymatically. Conditions for the two control modes are put forward and biochemical examples with the structure of enzyme-catalyzed dual-E controllers are discussed.


2021 ◽  
Author(s):  
Pallavi M Gosavi ◽  
Kevin C Ngan ◽  
Megan Yeo ◽  
Cindy Su ◽  
Jiaming Li ◽  
...  

Targeted protein degradation (TPD) holds immense promise for drug discovery but mechanisms of acquired resistance to degraders remain to be fully identified. Here we used CRISPR-suppressor scanning to identify mechanistic classes of drug resistance mutations to molecular glue degraders in GSPT1 and RBM39, neosubstrates targeted by E3 ligase substrate receptors cereblon and DCAF15, respectively. While many mutations directly alter the ternary complex heterodimerization surface, distal resistance sites were also identified. Several distal mutations in RBM39 led to modest decreases in degradation yet can enable cell survival, underscoring how small differences in degradation can lead to resistance. Integrative analysis of resistance sites across GSPT1 and RBM39 revealed varying levels of sequence conservation and mutational constraint that control the emergence of different resistance mechanisms, highlighting that many regions co-opted by TPD are inessential. Altogether, our study identifies common resistance mechanisms for molecular glue degraders and outlines a general approach to survey neosubstrate requirements necessary for effective degradation.


Author(s):  
Pooja Suvarna ◽  
Pinal Chaudhari ◽  
Sumit Birangal ◽  
Lakshmi Sruthi Mallela ◽  
Sanhita Roy ◽  
...  

2021 ◽  
Author(s):  
Junzhuo Liao ◽  
Xueqing Nie ◽  
Ilona Unarta ◽  
Spencer Ericksen ◽  
Weiping Tang

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce ubiquitination and subsequent degradation of proteins via formation of ternary complexes between an E3 ubiquitin ligase and a target protein. Rational design of PROTACs requires accurate knowledge of the native configuration of the PROTAC induced ternary complex. This study demonstrates that native and non-native ternary complex poses can be distinguished based on pose occupancy time in MD, where native poses exhibit longer occupancy times than non-native ones at both room and higher temperatures. Candidate poses are generated by MD sampling and pre-ranked by the classic MM/GBSA method. A specific heating scheme is then applied to induce ternary pose departure, generating an occupancy score and temperature score reflecting pose occupancy time and fraction. The scoring approach enables identification of the native pose in all the test systems. Beyond providing a relative rank of hypothetical poses of a given ternary system, the method could also provide empirical guidance to whether a given ternary pose is likely a native one or not. The success of the method is in part attributed to the dynamic nature of the pose departure analysis which accounts for solute entropic effects, typically neglected in the faster static pose scoring methods, while solute entropic contributions play a greater role in protein-protein interactions than in protein-ligand systems.


2021 ◽  
Author(s):  
Chengcheng Fan ◽  
Douglas C Rees

The ATP Binding Cassette (ABC) transporter of mitochondria (Atm) from Arabidopsis thaliana (AtAtm3) has been implicated in the maturation of cytosolic iron-sulfur proteins and heavy metal detoxification, plausibly by exporting glutathione derivatives. Using single-particle cryo-electron microscopy, we have determined structures of AtAtm3 in multiple conformational states. These structures not only provide a structural framework for defining the alternating access transport cycle, but also highlight an unappreciated feature of the glutathione binding site, namely the paucity of cysteine residues that could potentially form inhibitory mixed disulfides with glutathione. Despite extensive efforts, we were unable to prepare the ternary complex of AtAtm3 with bound GSSG and MgATP. A survey of structurally characterized type IV ABC transporters that includes AtAtm3 establishes that while nucleotides are found associated with all conformational states, they are effectively required to stabilize occluded and outward-facing conformations. In contrast, transport substrates have only been observed associated with inward-facing conformations. The absence of structures containing both nucleotide and transport substrate suggests that this ternary complex exists only transiently during the transport cycle.


2021 ◽  
Vol 584 ◽  
pp. 120561
Author(s):  
Shiwen Hu ◽  
Tongxu Liu ◽  
Yang Yang ◽  
Fangbai Li ◽  
Liping Fang

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