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Search for "binding site" in Full Text gives 174 result(s) in Beilstein Journal of Organic Chemistry.
Computational toolbox for the analysis of protein–glycan interactions
Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180
- /building the protein and the ligand in their optimal conformation (as discussed above), ii) predicting the protein binding site; iii) modelling the ligand into the protein binding site, iv) assessing binding affinity through sampling and scoring, as discussed in the following paragraphs [103]. Prediction
- of the protein binding site Over the years, structure-, sequence-, and homology/template- based methods have been employed to identify and predict carbohydrate-binding sites starting from the protein structure [104]. Recently, thanks to the fast development of machine learning techniques, new
- ligands into fragments, places, and scores them quickly in the binding site. The best fragments are then assembled to form the complete ligand, optimizing the generated conformations. FlexX's strengths include rapid and efficient exploration of the conformational space, handling ligand flexibility, a
The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)
Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162
- template, selecting the ligand building blocks with highest affinity and bringing them in proximity within the binding site. Building blocks are opportunely chosen to have complementary reactivity and therefore to react irreversibly within the binding site and assemble into the final ligand. Before the
Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry
Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147
- biocatalytic applications. The co-crystallisation of LahSB with bound SAH provides important details about the structure–function relationship, the substrate–enzyme interaction, and the cofactor binding site (Figure 5). This structural information, including the residues involved in binding, is essential for
Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA
Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132
- has a tetrameric structure, displays a high affinity for ᴅ-galactose (ᴅ-Gal, with Kd = 34 μM) and galactosides. The 3- and 4-hydroxy function on the ᴅ-Gal unit are involved in the coordination of Ca2+ in the binding site [5][6][7][8][32]. A large range of galactosyl conjugates have been synthetized
- rather similar Kd values. In order to rationalize this difference in binding mechanism, molecular models were obtained for selected low-energy conformations of E- and Z-isomers of a “model” scaffold of the para-azobenzene derivative in the binding site of LecA (Figure 5), by simple superpositioning of
Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain
Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131
- catalytic groove. The sequence logo of C0/C1-type KRs showed that some of them possess the catalytic Y (9), but such KRs instead possess mutation in NADPH binding site (Figure S3 in Supporting Information File 1). In C2-type KRs, we found that most C2-type KRs possessed the catalytic Y (9), but some
- either A2- or B2-KRs, but are likely to contain mutations in NADPH binding site [31]. Sequence logo analysis of KRC from γ- and δ-modules In the actinobacterial γ- and δ-modules, the stereochemical outcome of a KR is obscured by further dehydration catalyzed by DH. The dehydration mechanism by DH has
Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria
Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75
- [32]. We sought to identify the heme binding site, but AlphaFold does not model this. However, this AlphaFold model was predicted to bind a heme cofactor by the consensus modeling tool COACH [33]. This protein–ligand model exhibited steric clashes with the heme and protein side chains (data not shown
- NnlA model in Figure 5A. Several of these residues are nearby the predicted heme binding site, which may suggest their importance in NNG binding near the heme. However, many of these residues are either far from the heme or would not orient NNG towards the distal pocket of the heme. Future mutagenesis
Recent developments in the engineered biosynthesis of fungal meroterpenoids
Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50
- compounds (40, 43, 44, 47, 48, 50, 51, and 53–55) (Figure 7A). In addition, a structure-based mutagenesis study of SptF was performed to further amplify its catalytic potential. Firstly, the hydrophobic residues Ile63, Phe133, and Ile231, which compose the substrate binding site of SptF, were mutated. As a
- change their reaction products depending on the conformation of the terpenoid skeleton, the regiospecificity of the oxidation reaction can be modified by introducing random mutations in the substrate-binding site of αKG-dependent dioxygenase. The αKG-dependent dioxygenase AndA withdraws H-12 of
Switchable molecular tweezers: design and applications
Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45
- tweezers by the first equivalent generating an allosteric binding site specific to a second Hg2+ ion. While the addition of one equivalent of Hg2+ decreased the quantum yield to 0.09, the formation of a bis-coordinated [tweezers-Hg2]4+ complex resulted in a total luminescence quenching (quantum yield <10−3
- using metal complexes as switching units (Figure 20). This concept named “weak link approach” (WLA) [78] uses square planar d8-transition metal complexes with two hemilabile bidentate ligands composed of a strong binding site (phosphorus) and a weaker one (generally sulfur, oxygen, selenium, or nitrogen
- ) that is labile. By default, the complex is in a closed form with the functional units on each ligand facing each other due to the square planar geometry of the complex. By adding a first ancillary ligand (carbon monoxide, chloride,…) that strongly binds to the metal center, one weak binding site is
Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles
Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36
- the GPR receptor can aggravate the symptoms of myeloid leukemia. In contrast to most GPR84 agonists which contain long alkyl chains, BIMs are not lipophilic molecules, which allow them to bind to the GPR receptor via an allosteric binding site and modulate GPR84’s rate of expression [2]. One
Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin
Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31
- aligned the individual units of the tandem repeat CBM13 domains, indicated by the N-terminal (34-158) and C-terminal units (162-286) and compared those to the domains of ricin (Figure 1b). R-type lectins have a characteristic Q-x-W structural motif close to their binding site, which is highly conserved
- to elucidate the molecular mechanism that would enable the specific binding of C2-substituted galactose. The natural hypothesis here would be the creation of an additional pocket in the 3D structure of the binding site, accommodating the additional substituent at C2. However, as we observed little to
- (Val6 to Asp132) could be modelled, and unambiguous electron density permitted us to locate and model four cation binding sites (three in each structure) and one sugar binding site (Figure 4a,b and Figure S4, Supporting Information File 2). The complexed structures allowed us to shed light on the
Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions
Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11
- delivered without effect to the binding site, where the DNA-binding benzoquinolizinium ligand can then be generated as needed upon irradiation. Notably, the use of light for the activation of photo-controllable DNA ligands offers several advantages because it is easy to apply, traceless, and non-invasive
- within the binding site. The binding mode of the benzo[c]quinolizinium derivatives 3c,e–g with DNA was further examined with circular dichroism (CD) and linear dichroism (LD) spectroscopy (Figure 6 and Supporting Information File 1, Figures S12–S14). Hence, with increasing ligand-DNA ratio (LDR) weak
- binding angle α = 59° between the ligand 3f and the DNA helix, thus indicating a tilted orientation of the ligand relative to the DNA base pairs within the binding site. The DNA-binding ligands were also generated in situ in the presence of DNA. For that purpose, solutions of the styrylpyridines 2d–g and
Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling
Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144
- essential to explain their biological functions. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. We analyze the binding interactions between GAGs of three types (heparin, desulfated heparan sulfate, and chondroitin sulfate
- /pdb, [37]). The third complex is known to exist in two different binding poses which are experimentally well established. In this study, the umbrella sampling (US) approach is used to pull away a GAG ligand from the binding site and then pull it back in. The main focus of our study is to evaluate
- RS-REMD (replica exchange with repulsive scaling), an MD-based docking method [41], to assure proper binding poses of the whole ligand and ring puckering and to be consistent with further simulations. The docked ligands cover the binding site the same way as ligands in the experimental structures
Tying a knot between crown ethers and porphyrins
Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120
- -capped calix[4]pyrrole cavitand 4. The heteroditopic receptor had multiple binding sites, proving efficient in encapsulating a CsF ion pair. The calix[4]arene-crown-6-capped pocket was exploited as an excellent binding site for the Cs+ cation, whereas the calix[4]pyrrole was aligned to trap the fluoride
Synthesis of ether lipids: natural compounds and analogues
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
- ). The review of Lemaire et al., dedicated to the synthesis of glycerol ether, is complemental to this review article [57]. Of note, the review of Godfroid and Braquet attempted to decipher the binding site of PAF via a QSAR study [58]. 1.1 Synthesis of PAF and some building blocks The platelet
CO2 complexation with cyclodextrins
Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78
- change in spectrum of 7 provided 7 and CO2 compete for the binding site. To avoid problems with formation of hydrogencarbonate the experiments were conducted in a buffer at pH 3 where only a minor fraction of the carbonic acid (pKa1 = 3.6) is dissociated and since the hydration constant of CO2 is small
Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C
Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33
- pocket of the enzyme. In contrast, the S2 pocket preferably accommodates amino acids having short aliphatic side-chains, but also recognizes aromatic amino acids, preferably phenylalanine. To study the structural requirements of the S1 binding site of the enzyme, we synthesized a series of ten dipeptide
Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene
Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170
- , USA), to the two independent binding sites model. From the fit, the stoichiometry (n), binding enthalpy change (ΔH, kJ·mol−1), affinity constant (Ka, M−1), binding free energy change (ΔG, kJ·mol−1), and binding entropy change (ΔS, J·mol–1·K−1) for the first binding site were calculated. The
- thermodynamic parameters for the second binding site were not discussed but used to subtract the nonlinear residual heat at high molar ratios. Separate titration experiments of pure DMSO to the solution of tetracene in DMSO and DMSO to the solution of water in DMSO were carried out to account for potential
Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface
Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156
- 5) [21]. Gαi1 was selected as a positive control for subsequent studies because it can be expressed easily, has roughly 55% homology with the much more difficult to express Gαq [15], and chimeric proteins are available that have Gαi1 modified with a Gαq binding site for YM and FR [22]. R6A was
Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups
Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137
- area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational
- pairs of proteins (Figure 2b). Knowledge of the binding site is of critical importance for a potential bioanalytics application: if 1 would block one or both wells of the ω, it could prevent binding of ligand proteins, whereas a 1 binding site in the outer parts of the ω would not interfere with
- 1.5.2 [41]. To validate our method, we applied it to the QQJ-096/14-3-3/c-Raf complex for which the potential binding site was available from all-atom molecular dynamics simulations in a previous study [26]. Our results for this system are reported in the first part of the Supporting Information File 1
Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons
Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83
- determined from the optimized structures of compounds 21 and 22 (Figure 13a) by DFT suggest that pyridine is a better binding site than thiophene [43]. The effect of steric hindrance on the Lewis acid–base binding should not be ignored. If there is large steric hindrance of the Lewis basic molecules, it will
Structural basis for endoperoxide-forming oxygenases
Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71
- observed in typical Fe/2OG-dependent oxygenases (Figure 3A). The Fe(II) is coordinated by His129, Asp131, His205, and 2OG in the binary complex structure of FtmOx1 with 2OG. In this structure, Tyr224 is close to the putative oxygen binding site (Figure 3B). Furthermore, the variants in which Tyr224 is
Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis
Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62
- procedure developed by Sauvage on the basis of topological control [33] has found ample use in the preparation of rotaxane-based machines and devices [34]. A key element is a macrocyclic phenanthroline with an endotopic binding site as it precludes homoleptic complex formation. A further principle
(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia
Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144
- , with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1
- TKIs that are even more potent than IMT, such as nilotinib [6][7]. These drugs act as inhibitors at the ATP binding site in the inactive form of BCR-Abl-1, preventing the binding of the protein to ATP in a competitive manner and resulting in the interruption of the substrate phosphorylation process and
- interact with BCR-Abl-1 at the same binding site as IMT but show differences in the binding modes and with higher values of interaction energy. Compound 2c presented a MolDock value of −152.993 a.u. For compound 2d, the value was −152.127 a.u., and for compound 2g, it was −167.520 a.u. (Table 2
A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis
Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119
- relationships must be supported by ChIP-Seq evidence. Here, a nonlinear weighted sum called regulatory potential (RP) quantifies the strength of TF–gene interactions based on the proximity of TF binding site to the gene TSS and also the number of TF–gene binding interactions based experimentally detected ChIP
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
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