1,721,313 research outputs found
Interactions between proteins and Ru compounds of medicinal interest: A structural perspective
No full textRuthenium compounds have unique physicochemical properties that can be efficiently exploited in medicinal chemistry. These molecules can act using both DNA or enzymes as target. The molecular bases that govern DNA versus protein binding selectivity are not known, but a number of investigations has allowed one to obtain significant information on these recognition processes. Here we review some relevant crystallographic studies focused on the characterization of the interaction between proteins and selected ruthenium compounds of medicinal interest. Details of the interactions between Ru compounds and protein residues are described and the reactivity of the compounds towards different targets is compared with that observed analyzing analogous Pt-based drugs-protein adducts. Data provide important information that can be useful to a deeper understanding of the mechanism of actions of the analyzed compound
Metallomics: a primer of integrated biometal sciences
No full textA book review on the Book "metallomics:a primer of integrated biometal sceinces" by Maret
Molecular bases of protein halotolerance
No full textHalophilic proteins are stable and function at high salt concentration. Understanding how these molecules maintain their fold stable and avoid aggregation under harsh conditions is of great interest for biotechnological applications. This mini-review describes what is known about the molecular determinants of protein halotolerance. Comparisons between the sequences of halophilic/non-halophilic homologous protein pairs indicated that Asp and Glu are significantly more frequent, while Lys, Ile and Leu are less frequent in halophilic proteins. Homologous halophilic and non-halophilic proteins have similar overall structure, secondary structure content, and number of residues involved in the formation of H-bonds. On the other hand, on the halophilic protein surface, a decrease of nonpolar residues and an increase of charged residues are observed. Particularly, halophilic adaptation correlates with an increase of Asp and Glu, compensated by a decrease of basic residues, mainly Lys, on protein surface. A thermodynamic model, that provides a reliable explanation of the salt effect on the conformational stability of globular proteins, is presented
Heterogeneous nucleation helps the search for initial crystallization conditions of γ-glutamyl transpeptidase from Bacillus licheniformis
No full textHere, the crystallization and preliminary X-ray diffraction studies of Bacillus licheniformis γ-glutamyl transpeptidase (BlGT) are reported. The serendipitous finding of heterogeneous nucleants in the initial experiments provided the first crystallization conditions for the protein. Crystals were grown by hanging-drop vapour diffusion using a precipitant solution consisting of 20%(w/v) PEG 3350, 0.2 M magnesium chloride hexahydrate, 0.1 M Tris-HCl pH 8.2. The protein crystallized in the orthorhombic space group P2(1)2(1)2(1), with one heterodimer per asymmetric unit and unit-cell parameters a = 60.90, b = 61.97, c = 148.24 Å. The BlGT crystals diffracted to 2.95 Å resolution
γ-Glutamyltranspeptidases: sequence, structure, biochemical properties and biotechnological applications
No full textγ-Glutamyltranspeptidases (γ-GTs) are ubiquitous enzymes that catalyze the hydrolysis of γ-glutamyl bonds in glutathione and glutamine and the transfer of the released γ-glutamyl group to amino acids or short peptides. These enzymes are involved in glutathione metabolism and play critical roles in antioxidant defense, detoxification, and inflammation processes. Moreover, γ-GTs have been recently found to be involved in many physiological disorders, such as Parkinson’s disease and diabetes. In this review, the main biochemical and structural properties of γ-GTs isolated from different sources, as well as their conformational stability and mechanism of catalysis, are described and examined with the aim of contributing to the discussion on their structure–function relationships. Possible applications of γ-glutamyltranspeptidases in different fields of biotechnology and medicine are also discussed
Cisplatin binding to proteins: A structural perspective
No full textThe interactions of clinically established anticancer Pt-based drugs with proteins play crucial roles in Pt cellular uptake and biodistribution, as well as in determining side effects and resistance, thus affecting the overall pharmacological profile of this class of drugs. Here, we summarize a number of recent crystallographic studies of cisplatin/protein adducts that contribute unveiling the molecular basis for cisplatin-protein recognition. Details of each molecular structure are carefully and comparatively described; common trends and regularities occurring in the analyzed adducts are highlighted. Analysis of the structural features of its protein derivatives, integrated with selected results arising from the application of other biophysical methods on strictly related systems, allows an overall elucidation of the protein platination process and offers a more comprehensive understanding of the mode of action of cisplatin and its parent Pt-based drug
Interactions of carboplatin and oxaliplatin with proteins: Insights from X-ray structures and mass spectrometry studies of their ribonuclease A adducts
Full text linkOxaliplatin and carboplatin are two platinum(II) drugs in widespread clinical use for the treatment of various types of cancers; yet, structural information on their interactions with proteins is scarce. Here, the X-ray structures of the adducts formed upon reaction of carboplatin and oxaliplatin with bovine pancreatic ribonuclease (RNase A) are reported and compared with results obtained for the structure of the RNase A-cisplatin adduct derived from isomorphous crystals, under the same experimental conditions. Additional details on the binding mode of these metallodrugs toward RNase A are provided by electrospray ionization mass spectrometry (ESI MS) measurements, thus offering insight on the occurring metal-protein interactions. Notably, while carboplatin and cisplatin mainly bind the side chain of Met29, oxaliplatin also binds the side chains of Asp14, of catalytically important His119 and, to a lesser extent, of His105. On the basis of the available data, a likely mechanism for oxaliplatin hydrolysis and binding to the protein is proposed. These results are potentially useful for a better understanding of the biological chemistry, toxicity and side effects of this important class of antitumor agent
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