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Ligand

About: Ligand is a research topic. Over the lifetime, 67732 publications have been published within this topic receiving 1359684 citations. The topic is also known as: complexing agent & ligands.


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Journal ArticleDOI
TL;DR: In this article, the authors present an extended X-ray absorption fine structure (EXAFS) spectroscopic study of the molybdenum site of Desulfovibrio desulfuricans ATCC 27774 formate dehydrogenase (FDH) and show that under reducing conditions the selenosulfide group can be reduced.
Abstract: The mononuclear molybdenum enzymes all possess one or two molybdopterin cofactors coordinated to the molybdenum through the ditholene motif. Despite this common feature, they exhibit quite diverse functionality. The molybdenum enzymes previously have been described as all involving two-electron redox chemistry at molybdenum, coupled with the transfer of an oxygen atom from water via molybdenum to substrate, or the reverse. While these rules still appear to hold for most molybdenum enzymes, and for their close relatives the tungsten enzymes, it now seems that there are at least some exceptions. The recently discovered tungsten enzyme acetylene hydratase catalyzes a net hydration reaction, rather than a redox one. Very recently it has been shown that formate oxidation to CO{sub 2} by Eschericia coli formate dehydrogenase H (FDH{sub H}) does not involve oxygen atom transfer. This enzyme has also been shown to possess a potentially redox-active selenosulfide ligand to molybdenum, with the selenosulfide sulfur probably being one of the sulfurs of the cofactor dithiolene. The authors present an extended X-ray absorption fine structure (EXAFS) spectroscopic study of the molybdenum site of Desulfovibrio desulfuricans ATCC 27774 formate dehydrogenase (FDH) and show that under reducing conditions the selenosulfide group can be reduced. This is themore » first observation of ligand-based redox chemistry in a molybdenum enzyme.« less

39 citations

Journal ArticleDOI
TL;DR: In contrast to many other heme proteins including the globins, the ferroheme state was found to be extremely sensitive to O2, which is a consequence of the much lower reduction potential of the NPs, so that the 1‐electron reduction of O2 to O’−2 becomes a thermodynamically favored process.
Abstract: Nitrophorins (NPs) comprise a unique class of heme proteins used by the blood-sucking insect Rhodnius prolixus to deliver the signaling gas molecule NO into the blood vessel of a host during feeding. Upon NO release, histamine can be scavenged by coordination to the heme iron. Although the protein is of similar size as the mammalian globin monomers and shares the same cofactor and proximal histidine coordination, nitrophorin structure, in contrast, is almost entirely composed of a β-barrel. Comparison of the NO and histamine association constants with the concentrations of both compounds invivo raises concerns about the very simple ligand release model in case of at least some of the NPs. Therefore, novel functionalities of the NPs were sought. As a result, catalysis of the nitrite disproportionation reaction was found, which leads to the formation of NO with nitrite as the sole substrate. This is the first example of a ferriheme protein that can perform this reaction. Furthermore, although NPs stabilize the ferriheme state, a peroxidase reactivity of the cofactor involving the higher oxidation state iron (Compound I/II) was studied with the potential to catalyze the oxidation of histamine and norepinephrine. In contrast to many other heme proteins including the globins, the ferroheme state was found to be extremely sensitive to O(2) , which is a consequence of the much lower reduction potential of the NPs, so that the 1-electron reduction of O(2) to O (•-)(2) becomes a thermodynamically favored process. Altogether, the detailed study of the NPs gives insight into the structure-function relationships required for the targeted delivery of diatomic gas molecules in biology. Moreover, the comparison of the structure-function relationships of the NPs (NO transporters) with those of the globins (O(2) transporters) will help to elucidate the architectural requirement for the respective tasks.

39 citations

Journal ArticleDOI
TL;DR: The 2B4 active site is able to accommodate small ligands by moving only a small number of side chains, suggesting that ligand reorientation is energetically favored over protein conformational changes for binding of these similarly sized molecules.
Abstract: Prior X-ray crystal structures of rabbit cytochrome P450 2B4 (2B4) in complexes with various imidazoles have demonstrated markedly different enzyme conformations depending on the size of the inhibitor occupying the active site. In this study, structures of 2B4 were determined with the antiplatelet drugs clopidogrel and ticlopidine, which were expected to have greater freedom of movement in the binding pocket. Ticlopidine could be modeled into the electron density maps in two distinct orientations, both of which are consistent with metabolic data gathered with other mammalian P450 enzymes. Results of ligand docking and heme-induced NMR relaxation of drug protons showed that ticlopidine was preferentially oriented with the chlorophenyl group closest to the heme. Because of its stereocenter, clopidogrel was easier to fit in the electron density and exhibited a single orientation, which points the chlorophenyl ring toward the heme. The C(α) traces of both complexes aligned very well with each other and revealed a compact, closed structure that resembles the conformation observed in two previously determined 2B4 structures with the small molecule inhibitors 4-(4-chlorophenyl)imidazole and 1-(4-chlorophenyl)imidazole. The 2B4 active site is able to accommodate small ligands by moving only a small number of side chains, suggesting that ligand reorientation is energetically favored over protein conformational changes for binding of these similarly sized molecules. Adjusting both protein conformation and ligand orientation in the active site gives 2B4 the flexibility to bind to the widest range of molecules, while also being energetically favorable.

39 citations

Journal ArticleDOI
TL;DR: Cytotoxicity studies reveal that the dinuclear ruthenium complexes are dramatically less active against cancer cell lines than the recently reported supramolecular cylinders prepared from the same bis(pyridylimine) ligand.
Abstract: Enantiopure dinuclear ruthenium polypyridyl complexes of the form [Ru2(LL)4L1](PF6)4 (LL = 2,2′-bipyridine (bpy) or 1,10-phenanthroline (phen); L1 = C25H20N4 a bis(pyridylimine) ligand containing a diphenylmethane spacer) have been synthesized using the chiral building blocks cis-[Ru(bpy)2(py)2]2+ and cis-[Ru(phen)2(py)2]2+. These dinuclear ruthenium complexes have been characterised using NMR, mass spectrometry, UV-visible absorbance, circular dichroism and linear dichroism. The compounds exhibit good photo and thermal stability. The extinction coefficient for the bpy complex at 478 nm is e478 = 15700 mol−1 cm−1 dm3 and for the phen complex is e478 = 24900 mol−1 cm−1 dm3. Both complexes have their longest wavelength (metal to ligand charge transfer) transition predominantly x/y (short axis)-polarised while the transitions at shorter wavelength are a mixture of x/y and z-polarisations, similar to both the copper helicate and iron triple helicate studied previously. Cytotoxicity studies reveal that the compounds are dramatically less active against cancer cell lines than the recently reported supramolecular cylinders prepared from the same bis(pyridylimine) ligand.

39 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202275
20212,355
20202,463
20192,413
20182,466
20172,498