Interactions and electron-transfer reactions between metalloproteins

Electron-transfer reactions are essential for life. Because metalloproteins are involved in electron transport in the cell, it is important to understand the factors that affect recognition, interaction, and reactions of these electron carriers. Cytochrome c is well-characterized electron-carrier protein. The heme protein cytochrome c and the blue-copper protein plastocyanin are well suited for kinetic and mechanistic studies since their structures are known in detail;We investigated the effects of site-directed mutations and viscosity on rate-limiting rearrangement within the complex of cytochrome c and plastocyanin and identified the reactive configuration of the complex. In the reactive configuration of the complex cytochrome c heme edge is between plastocyanin acidic and hydrophobic patch. The reactive intermediate is formed upon transfer of an electron in the reaction of cytochrome c and plastocyanin. The intermediate is zinc cytochrome c cation radical which exhibits different reactivity from the native iron(III) form of the protein. The reorganization energy and electron self-exchange rate constant of the zinc cytochrome c cation radical show that methionine, ligand in iron form of the protein, is uncoordinated in the zinc form of the protein;We extended the proton-linkage model so it can give information about individual proteins and even about amino-acid residues involved in protein association. We extract from the experimental results the composite pK a values, both in separate and in combined proteins, of groups of residues that change their protonation state upon protein association. The extended model was applied to intricate effects of pH on association of cytochrome c with wild-type and several mutant forms of plastocyanin. We extract from the experimental results the composite pKa values, both in separate and in combined proteins, of groups of residues that change their protonation state upon protein association. Interpretation of these parameters revealed general and specific features of the protein-protein interaction;The effects of pH on protein rearrangement were studied. The rearrangement is independent of pH and amino acid side chains in the acidic patch of plastocyanin are deprotonated in the complex of cytochrome c and plastocyanin. Study of effects of pH on a dynamic protein complex allows inferences about the protonation states of particular side chains

Zagreb earthquake of 22 March 2020 – preliminary report on seismologic aspects and damage to buildings

U radu su opisane bitne značajke i glavne posljedice potresa magnitude 5,5 koji je u jeku pandemije virusa COVID-19 zadesio Zagreb i okolicu. Premda je potres, seizmološki gledano, bio umjerene magnitude, prouzročio je gubitak jednoga života i veliku materijalnu štetu. Napravljen je pregled stanja prije trešnje te prikaz lokacije, seizmičke aktivnosti i organizacije pregleda zgrada. Grubo su razvrstani podaci o oštećenjima, s težištem na povijesnoj jezgri i četvrtima blizu epicentra. Na kraju su istaknute nužne aktivnosti koje je odavno trebalo provesti, s nadom da će ih ovaj potres potaknuti.Significant characteristics and main consequences of the 5.5 magnitude earthquake that struck Zagreb and its surroundings in the midst of the COVID-19 pandemic are presented in the paper. Although, from the seismologic aspect, the earthquake was of moderate magnitude, it caused the loss of one life and considerable material damage. An overview of the situation before the quake is given, and information about the location, seismic activity, and organisation of building inspection activity, is presented. The data on damage are roughly classified, with the focus on historic core of the city and districts situated close to the epicentre. A strong emphasis is placed on indispensable activities that should have been carried out a long time ago, in the hope that they will be prompted by this earthquake

Interactions and electron-transfer reactions between metalloproteins

Electron-transfer reactions are essential for life. Because metalloproteins are involved in electron transport in the cell, it is important to understand the factors that affect recognition, interaction, and reactions of these electron carriers. Cytochrome c is well-characterized electron-carrier protein. The heme protein cytochrome c and the blue-copper protein plastocyanin are well suited for kinetic and mechanistic studies since their structures are known in detail;We investigated the effects of site-directed mutations and viscosity on rate-limiting rearrangement within the complex of cytochrome c and plastocyanin and identified the reactive configuration of the complex. In the reactive configuration of the complex cytochrome c heme edge is between plastocyanin acidic and hydrophobic patch. The reactive intermediate is formed upon transfer of an electron in the reaction of cytochrome c and plastocyanin. The intermediate is zinc cytochrome c cation radical which exhibits different reactivity from the native iron(III) form of the protein. The reorganization energy and electron self-exchange rate constant of the zinc cytochrome c cation radical show that methionine, ligand in iron form of the protein, is uncoordinated in the zinc form of the protein;We extended the proton-linkage model so it can give information about individual proteins and even about amino-acid residues involved in protein association. We extract from the experimental results the composite pK a values, both in separate and in combined proteins, of groups of residues that change their protonation state upon protein association. The extended model was applied to intricate effects of pH on association of cytochrome c with wild-type and several mutant forms of plastocyanin. We extract from the experimental results the composite pKa values, both in separate and in combined proteins, of groups of residues that change their protonation state upon protein association. Interpretation of these parameters revealed general and specific features of the protein-protein interaction;The effects of pH on protein rearrangement were studied. The rearrangement is independent of pH and amino acid side chains in the acidic patch of plastocyanin are deprotonated in the complex of cytochrome c and plastocyanin. Study of effects of pH on a dynamic protein complex allows inferences about the protonation states of particular side chains.</p

Floor structures in standard building construction

Prikazane su osnovne vrste stropnih konstrukcija koje se najčešće primjenjuju u visokogradnji. Analizirana je primjene uobičajenih tipova stropova za veće raspone, posebno problemi graničnih stanja uporabljivosti. Navedene su tablice i dijagrami za projektiranje fert-stropova prema graničnom stanju nosivosti te prema više kriterija progiba. Upozoreno je na najčešće pogreške pri projektiranju i izvedbi. Analizirane su mogućnosti izvedbe stropnih konstrukcija većih raspona.Basic types of floor structures commonly used in building construction are presented. The use of standard types of floors for greater spans is analyzed, and a particular emphasis is placed on problems relating to limit state of serviceability. Tables and diagrams for the design of semi-prefabricated floor systems based on ultimate limit state and several deflection criteria, are presented. Authors caution that errors are most frequently made at the stages of design and realization. Possibilities for realizing floor structures of greater span are analyzed

Original scientific paper

Effects of pH on kinetics of the structural rearrangement that gates the electron-transfer reaction between zinc cytochrome c and plastocyanin. Analysis of protonation states in a diprotein complex

Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions

Selected tetrahydropyrimidines (THPMs) were investigated by means of cytotoxic activities on selected cancer (HeLa, A549, and LS174) and non-cancerous cell lines (MRC-5). Among evaluated compounds, two of them ( B7 and B8 ) showed good cytotoxic activity on the tested cell lines and were selected for fur- ther evaluation that included mechanism of action, DNA and BSA interactions and molecular docking study. Calculated parameters from fluorescence quenching studies indicated that B7 and B8 bind on mi- nor groove of DNA and have great ability to bind on carrier protein. Three-dimensional quantitative struc- ture anti-HeLa activity study was performed with data set of THPMs. Molecular Interaction Fields were used to derive Grid independent descriptors (GRIND), as independent variables in Pentacle software. The quality and predictive capacity of the model was proved by internal statistical parameters: R 2 = 0.992, Q 2 = 0.51, as well as external parameters such as R 2 pred = 0.804 and r m 2 , r / 2 m and r 2 m , that were higher than 0.5. The structural determinants significant for anti-HeLa activity of compounds were identified by using developed 3D-QSAR model. Interpretation of the most impactful GRIND variables on the anti-HeLa activity generated several hypotheses for design of novel and more potent anti-HeLa tetrahydropyrim- idines. Additional molecular targets for the most active synthesized derivatives ( B7 and B8 ) are predicted by use of online web-based tool-SwissTargetPrediction

Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels

In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography. © 2019 Elsevier Inc