Development of the ELTE X-ray cristallographic infrastructure to investigate and fine-tune the structure and interactions of biomachromolecules and biologically active molecules (Q3958268): Difference between revisions
Jump to navigation
Jump to search
(Changed an Item: add summary) |
(Changed an Item: Adding English translations) |
||||||||||||||
| Property / summary | |||||||||||||||
A) OBJECTIVE No. 2 — The aim of the project is to promote domestic structural chemistry and structural biological research, to support the launch of new cutting-edge basic research and innovation activities by expanding the existing X-ray diffraction infrastructure. The current infrastructure consists of equipped crystallising laboratories, crystallising robot and an outdated diffractometer suitable for protein structure testing. The planned development, the acquisition of a diffractometer with a rotary annode and state-of-the-art hybrid pixel detector, would make it possible to extend the range of applications with the help of a new device with unique sensitivity in Hungary. The importance of X-ray diffraction RESEARCHs — The well-regulated interaction network of molecules plays an unavoidable role in the functioning of the living organism, including the interactions and permanent or transient complexes of proteins with each other and with other molecules. Three-dimensional representation plays a major role in understanding these processes. X-ray diffraction — where the success of the measurement, the information content of the measured data depends both on the quality of the tested crystal and on the state-of-the-art of the diffraction apparatus, is one of the main tools for spatial examination of molecules, molecular complexes and interactions in atomic detail. The Focal Points of RESEARCH — The project brings together interdisciplinary research, focusing on intermolecular interactions, atomic characterisation and design of spatial interaction patterns in protein complexes and small molecule crystals. One of the main objectives of our research is to better understand protein function and loanable protein networks, to map the altered structural-interaction properties of protein variants and protein changes associated with diseases, to help design ligands and proteins (liable peptide motifs). 1) Chemical modification of protein related to diseases (e.g. oxidation is the DJ-1 protein that performs the protective function against Parkinson’s disease; point mutations in the case of an enzyme responsible for the production of pseudouridine involved in fine-tuning of the RNA structure) and understanding of the structural and interaction shifts resulting from these, in order to clarify the structural elements of the function. In addition, our aim is to provide effective assistance in the design of specific ligands (in combination with highly permeable methods) and in the use of advanced ligands as active substance candidates or molecular sensors (e.g. DJ-1 and D-aminoacid oxidase). The diffractometer to be obtained also routinely collects high-quality measurement data from less dispersing crystals, which speeds up the design process. 2) By specific inhibition of the abnormal activation of the immune system, inhibitor molecules that can be used in medicine or in a more detailed examination of activation pathways (e.g. complement system) can be developed. With the X-ray diffraction infrastructure, we want to understand the specificity and selectivity of these new protein inhibitor molecules developed with directional evolution. 3) Between protein-protein interaction patterns, the interactions of node proteins are also significant from a medical point of view, which are characterised by the recognition of various loanable motives, thereby significantly affecting physiological processes by influencing the operation of several protein partners (e.g. S100 proteins involved in metastasis, or MAP kinases, tyrosine kinases that control cell division and motion processes involved in signal transmission processes). The chemical change of protein borrowable surfaces (e.g. phosphorylation) is universal in the regulation of signal transmission processes, often in the background of pathological processes. 4) In the case of self-organised, multimers-generating proteins that separate the chemical reaction they catalyse from the outside world by a cavity system, thus potential targets for biotechnological applications, our aim is to identify and characterise structural details important for protein self-organisation (oligopeptidases). 5) By defining the structure of small molecules, one of our goals is the high precision determination of molecules, from which we can infer the change of reactivity within a series of compounds in the case of biologically active compounds (e.g. ferrocene derivatives, compounds with cytostatic action). 6) Selective, kiral recognition of loanable partners is essential in the functioning of biological systems. In the production of bioactive molecules, therefore, effective separation of mirror image pairs (chiral separation) is of great importance, the most effective method of which is usually the chiral recognition generated by crystallisation in the solid phase. On the other hand, the geometric characteristics of directional interactions and shape fit, which play an important role in chiral recog... (English) | |||||||||||||||
| Property / summary: A) OBJECTIVE No. 2 — The aim of the project is to promote domestic structural chemistry and structural biological research, to support the launch of new cutting-edge basic research and innovation activities by expanding the existing X-ray diffraction infrastructure. The current infrastructure consists of equipped crystallising laboratories, crystallising robot and an outdated diffractometer suitable for protein structure testing. The planned development, the acquisition of a diffractometer with a rotary annode and state-of-the-art hybrid pixel detector, would make it possible to extend the range of applications with the help of a new device with unique sensitivity in Hungary. The importance of X-ray diffraction RESEARCHs — The well-regulated interaction network of molecules plays an unavoidable role in the functioning of the living organism, including the interactions and permanent or transient complexes of proteins with each other and with other molecules. Three-dimensional representation plays a major role in understanding these processes. X-ray diffraction — where the success of the measurement, the information content of the measured data depends both on the quality of the tested crystal and on the state-of-the-art of the diffraction apparatus, is one of the main tools for spatial examination of molecules, molecular complexes and interactions in atomic detail. The Focal Points of RESEARCH — The project brings together interdisciplinary research, focusing on intermolecular interactions, atomic characterisation and design of spatial interaction patterns in protein complexes and small molecule crystals. One of the main objectives of our research is to better understand protein function and loanable protein networks, to map the altered structural-interaction properties of protein variants and protein changes associated with diseases, to help design ligands and proteins (liable peptide motifs). 1) Chemical modification of protein related to diseases (e.g. oxidation is the DJ-1 protein that performs the protective function against Parkinson’s disease; point mutations in the case of an enzyme responsible for the production of pseudouridine involved in fine-tuning of the RNA structure) and understanding of the structural and interaction shifts resulting from these, in order to clarify the structural elements of the function. In addition, our aim is to provide effective assistance in the design of specific ligands (in combination with highly permeable methods) and in the use of advanced ligands as active substance candidates or molecular sensors (e.g. DJ-1 and D-aminoacid oxidase). The diffractometer to be obtained also routinely collects high-quality measurement data from less dispersing crystals, which speeds up the design process. 2) By specific inhibition of the abnormal activation of the immune system, inhibitor molecules that can be used in medicine or in a more detailed examination of activation pathways (e.g. complement system) can be developed. With the X-ray diffraction infrastructure, we want to understand the specificity and selectivity of these new protein inhibitor molecules developed with directional evolution. 3) Between protein-protein interaction patterns, the interactions of node proteins are also significant from a medical point of view, which are characterised by the recognition of various loanable motives, thereby significantly affecting physiological processes by influencing the operation of several protein partners (e.g. S100 proteins involved in metastasis, or MAP kinases, tyrosine kinases that control cell division and motion processes involved in signal transmission processes). The chemical change of protein borrowable surfaces (e.g. phosphorylation) is universal in the regulation of signal transmission processes, often in the background of pathological processes. 4) In the case of self-organised, multimers-generating proteins that separate the chemical reaction they catalyse from the outside world by a cavity system, thus potential targets for biotechnological applications, our aim is to identify and characterise structural details important for protein self-organisation (oligopeptidases). 5) By defining the structure of small molecules, one of our goals is the high precision determination of molecules, from which we can infer the change of reactivity within a series of compounds in the case of biologically active compounds (e.g. ferrocene derivatives, compounds with cytostatic action). 6) Selective, kiral recognition of loanable partners is essential in the functioning of biological systems. In the production of bioactive molecules, therefore, effective separation of mirror image pairs (chiral separation) is of great importance, the most effective method of which is usually the chiral recognition generated by crystallisation in the solid phase. On the other hand, the geometric characteristics of directional interactions and shape fit, which play an important role in chiral recog... (English) / rank | |||||||||||||||
Normal rank | |||||||||||||||
| Property / summary: A) OBJECTIVE No. 2 — The aim of the project is to promote domestic structural chemistry and structural biological research, to support the launch of new cutting-edge basic research and innovation activities by expanding the existing X-ray diffraction infrastructure. The current infrastructure consists of equipped crystallising laboratories, crystallising robot and an outdated diffractometer suitable for protein structure testing. The planned development, the acquisition of a diffractometer with a rotary annode and state-of-the-art hybrid pixel detector, would make it possible to extend the range of applications with the help of a new device with unique sensitivity in Hungary. The importance of X-ray diffraction RESEARCHs — The well-regulated interaction network of molecules plays an unavoidable role in the functioning of the living organism, including the interactions and permanent or transient complexes of proteins with each other and with other molecules. Three-dimensional representation plays a major role in understanding these processes. X-ray diffraction — where the success of the measurement, the information content of the measured data depends both on the quality of the tested crystal and on the state-of-the-art of the diffraction apparatus, is one of the main tools for spatial examination of molecules, molecular complexes and interactions in atomic detail. The Focal Points of RESEARCH — The project brings together interdisciplinary research, focusing on intermolecular interactions, atomic characterisation and design of spatial interaction patterns in protein complexes and small molecule crystals. One of the main objectives of our research is to better understand protein function and loanable protein networks, to map the altered structural-interaction properties of protein variants and protein changes associated with diseases, to help design ligands and proteins (liable peptide motifs). 1) Chemical modification of protein related to diseases (e.g. oxidation is the DJ-1 protein that performs the protective function against Parkinson’s disease; point mutations in the case of an enzyme responsible for the production of pseudouridine involved in fine-tuning of the RNA structure) and understanding of the structural and interaction shifts resulting from these, in order to clarify the structural elements of the function. In addition, our aim is to provide effective assistance in the design of specific ligands (in combination with highly permeable methods) and in the use of advanced ligands as active substance candidates or molecular sensors (e.g. DJ-1 and D-aminoacid oxidase). The diffractometer to be obtained also routinely collects high-quality measurement data from less dispersing crystals, which speeds up the design process. 2) By specific inhibition of the abnormal activation of the immune system, inhibitor molecules that can be used in medicine or in a more detailed examination of activation pathways (e.g. complement system) can be developed. With the X-ray diffraction infrastructure, we want to understand the specificity and selectivity of these new protein inhibitor molecules developed with directional evolution. 3) Between protein-protein interaction patterns, the interactions of node proteins are also significant from a medical point of view, which are characterised by the recognition of various loanable motives, thereby significantly affecting physiological processes by influencing the operation of several protein partners (e.g. S100 proteins involved in metastasis, or MAP kinases, tyrosine kinases that control cell division and motion processes involved in signal transmission processes). The chemical change of protein borrowable surfaces (e.g. phosphorylation) is universal in the regulation of signal transmission processes, often in the background of pathological processes. 4) In the case of self-organised, multimers-generating proteins that separate the chemical reaction they catalyse from the outside world by a cavity system, thus potential targets for biotechnological applications, our aim is to identify and characterise structural details important for protein self-organisation (oligopeptidases). 5) By defining the structure of small molecules, one of our goals is the high precision determination of molecules, from which we can infer the change of reactivity within a series of compounds in the case of biologically active compounds (e.g. ferrocene derivatives, compounds with cytostatic action). 6) Selective, kiral recognition of loanable partners is essential in the functioning of biological systems. In the production of bioactive molecules, therefore, effective separation of mirror image pairs (chiral separation) is of great importance, the most effective method of which is usually the chiral recognition generated by crystallisation in the solid phase. On the other hand, the geometric characteristics of directional interactions and shape fit, which play an important role in chiral recog... (English) / qualifier | |||||||||||||||
point in time: 9 February 2022
| |||||||||||||||
Revision as of 18:46, 9 February 2022
Project Q3958268 in Hungary
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Development of the ELTE X-ray cristallographic infrastructure to investigate and fine-tune the structure and interactions of biomachromolecules and biologically active molecules |
Project Q3958268 in Hungary |
Statements
237,561,000 forint
0 references
865,870.442 Euro
0.0027336256 Euro
15 December 2021
0 references
316,748,000.0 forint
0 references
74.999999 percent
0 references
19 April 2018
0 references
31 December 2020
0 references
EÖTVÖS LORÁND TUDOMÁNYEGYETEM
0 references
47°29'30.62"N, 18°58'44.15"E
0 references
A) CÉLKITŰZÉS - A projekt célja a hazai szerkezeti kémiai és szerkezeti biológiai kutatások elősegítése, új élvonalbeli alapkutatási és innovációs tevékenységek indításának támogatása a meglévő röntgendiffrakciós infrastruktúra bővítésével. A jelenlegi infrastruktúra felszerelt kristályosító laboratóriumokból, kristályosító robotból és egy fehérje szerkezetvizsgálatra alkalmas, de elavult diffraktométerből áll. A tervezett fejlesztés, egy forgóanóddal és a legkorszerűbb hibrid pixel detektorral ellátott diffraktométer beszerzés, lehetővé tenné az alkalmazások körének kiterjesztését a Magyarországon egyedülálló érzékenységgel rendelkező új készülék segítségével. A RÖNTGENDIFFRAKCIÓS KUTATÁSOK JELENTŐSÉGE - Az élő szervezet működésében kikerülhetetlen szerepet kap a molekulák finoman szabályozott kölcsönhatási hálózata – ezek között is kitüntetett szerepet kapnak a fehérjék egymással és más molekulákkal létrejövő kölcsönhatásai, állandó vagy tranziens komplexei. A három-dimenziós megjelenítés nagy szerepet játszik e folyamatok megértésében. A molekulák, molekula komplexek és kölcsönhatások atomi részletességű térbeli vizsgálatának egyik fő eszköze a röntgendiffrakció – ahol a mérés sikere, a mért adatok információtartalma a vizsgált kristály minőségén, és a diffrakciós készülék korszerűségén egyaránt múlik. A KUTATÁS FÓKUSZPONTJAI - A projekt interdiszciplináris kutatásokat fog össze, fókuszában intermolekuláris kölcsönhatások, térbeli kölcsönhatás-mintázatok atomi szintű jellemzése és tervezése áll fehérjék komplexeiben, valamint kismolekulás kristályokban. Az kutatásaink egyik fő célja a fehérjefunkció és kölcsönható fehérje-hálózatok jobb megértése, betegségekkel összefüggő fehérjevariánsok és fehérjemódosulatok megváltozott szerkezeti-kölcsönhatási tulajdonságainak feltérképezése ligandumok és fehérjék (kölcsönható peptid motívumok) tervezésének segítése. 1) A fehérje betegségekkel összefüggő kémiai módosulása (pl. oxidáció a Parkinson-kór elleni védőfunkciót betöltő DJ-1 fehérje; pontmutációk az RNS szerkezet finomhangolásában szerepet játszó pszeudo-uridin előállításáért felelős enzim esetén) és az ezek hatására létrejövő szerkezeti- és kölcsönhatás-átrendeződések megértése a funkció szerkezeti elemeinek tisztázása miatt kiemelt fontosságú. Emellett célunk, hogy hatékony segítséget nyújtsunk specifikusan kötődő ligandumok tervezésében (nagy áteresztőképességű módszerekkel kombinálva) majd a továbbfejlesztett ligandumok hatóanyag-jelöltként vagy molekuláris szenzorként való hasznosításában (pl. DJ-1, és a D-aminosav oxidáz). A beszerezni kívánt diffraktométerrel kevésbé jól szóró kristályokról is rutinszerűen jó minőségű mérési adatok gyűjthetők, ami meggyorsítja a tervezési folyamatot. 2) Az immunrendszer kóros aktiválódásának specifikus gátlásával gyógyászatban vagy az aktiválódási útvonalak (pl. komplement rendszer) részletesebb vizsgálatában alkalmazható inhibitor molekulák fejleszthetők ki. A röntgendiffrakciós infrastruktúrával ezeknek az irányított evolúcióval kifejlesztendő, és kifejlesztett új fehérje inhibitormolekuláknak a specificitását és szelektivitását szeretnénk megérteni kémiai szempontból. 3) A fehérje-fehérje kölcsönhatás mintázatok között gyógyászati szempontból is jelentősek a csomóponti fehérjék kölcsönhatásai, amelyek jellemzője, hogy különféle kölcsönható motívumokat felismernek, ezáltal több fehérjepartner működésének befolyásolásán keresztül az élettani folyamatokat jelentősen befolyásolják (pl. a metasztázisban szerepet játszó S100 fehérjék, vagy a jelátviteli folyamatokban résztvevő MAP kinázok, sejtosztódási és -mozgási folyamatokat szabályozó tirozin kinázok). A fehérje kölcsönható felszínek kémiai megváltoztatása (pl. foszforiláció) univerzális a jelátviteli folyamatok szabályozásában, gyakran kóros folyamatok hátterében is ez áll. 4) Az önszerveződő, multimereket létrehozó fehérjék esetén, amelyek üregrendszerrel különítik el az általuk katalizált kémiai reakciót a külvilágtól, ezáltal biotechnológiai alkalmazások potenciális célpontjai, célunk a fehérje-önszerveződés szempontjából fontos szerkezeti részletek azonosítása és jellemzése (oligopeptidázok). 5) Kismolekulák szerkezet-meghatározásával egyik célunk a molekulageometria nagy pontosságú meghatározása, amiből következtethetünk egy vegyületsorozaton belül a reaktivitás változására biológiailag aktív vegyületek esetén (pl. ferrocénszármazékok, citosztatikus hatású vegyületek). 6) A kölcsönható partnerek szelektív, királis felismerése a biológiai rendszerek működésében alapvető fontosságú. Bioaktív molekulák előállításakor ezért nagy fontosságú a képződő tükörképi párok hatékony elválasztása (királis elválasztás), amelynek leghatékonyabb módszere általában a szilárd fázisban, kristályosodás által keltett királis felismerés. Másfelől a királis felismerésben fontos szerepet játszó irányított kölcsönhatások, alak szerinti illeszkedés geometriai jellemzői jó minőségű kismolekulás kristályokon tanulmányozhatók részletesen. (Hungarian)
0 references
A) OBJECTIVE No. 2 — The aim of the project is to promote domestic structural chemistry and structural biological research, to support the launch of new cutting-edge basic research and innovation activities by expanding the existing X-ray diffraction infrastructure. The current infrastructure consists of equipped crystallising laboratories, crystallising robot and an outdated diffractometer suitable for protein structure testing. The planned development, the acquisition of a diffractometer with a rotary annode and state-of-the-art hybrid pixel detector, would make it possible to extend the range of applications with the help of a new device with unique sensitivity in Hungary. The importance of X-ray diffraction RESEARCHs — The well-regulated interaction network of molecules plays an unavoidable role in the functioning of the living organism, including the interactions and permanent or transient complexes of proteins with each other and with other molecules. Three-dimensional representation plays a major role in understanding these processes. X-ray diffraction — where the success of the measurement, the information content of the measured data depends both on the quality of the tested crystal and on the state-of-the-art of the diffraction apparatus, is one of the main tools for spatial examination of molecules, molecular complexes and interactions in atomic detail. The Focal Points of RESEARCH — The project brings together interdisciplinary research, focusing on intermolecular interactions, atomic characterisation and design of spatial interaction patterns in protein complexes and small molecule crystals. One of the main objectives of our research is to better understand protein function and loanable protein networks, to map the altered structural-interaction properties of protein variants and protein changes associated with diseases, to help design ligands and proteins (liable peptide motifs). 1) Chemical modification of protein related to diseases (e.g. oxidation is the DJ-1 protein that performs the protective function against Parkinson’s disease; point mutations in the case of an enzyme responsible for the production of pseudouridine involved in fine-tuning of the RNA structure) and understanding of the structural and interaction shifts resulting from these, in order to clarify the structural elements of the function. In addition, our aim is to provide effective assistance in the design of specific ligands (in combination with highly permeable methods) and in the use of advanced ligands as active substance candidates or molecular sensors (e.g. DJ-1 and D-aminoacid oxidase). The diffractometer to be obtained also routinely collects high-quality measurement data from less dispersing crystals, which speeds up the design process. 2) By specific inhibition of the abnormal activation of the immune system, inhibitor molecules that can be used in medicine or in a more detailed examination of activation pathways (e.g. complement system) can be developed. With the X-ray diffraction infrastructure, we want to understand the specificity and selectivity of these new protein inhibitor molecules developed with directional evolution. 3) Between protein-protein interaction patterns, the interactions of node proteins are also significant from a medical point of view, which are characterised by the recognition of various loanable motives, thereby significantly affecting physiological processes by influencing the operation of several protein partners (e.g. S100 proteins involved in metastasis, or MAP kinases, tyrosine kinases that control cell division and motion processes involved in signal transmission processes). The chemical change of protein borrowable surfaces (e.g. phosphorylation) is universal in the regulation of signal transmission processes, often in the background of pathological processes. 4) In the case of self-organised, multimers-generating proteins that separate the chemical reaction they catalyse from the outside world by a cavity system, thus potential targets for biotechnological applications, our aim is to identify and characterise structural details important for protein self-organisation (oligopeptidases). 5) By defining the structure of small molecules, one of our goals is the high precision determination of molecules, from which we can infer the change of reactivity within a series of compounds in the case of biologically active compounds (e.g. ferrocene derivatives, compounds with cytostatic action). 6) Selective, kiral recognition of loanable partners is essential in the functioning of biological systems. In the production of bioactive molecules, therefore, effective separation of mirror image pairs (chiral separation) is of great importance, the most effective method of which is usually the chiral recognition generated by crystallisation in the solid phase. On the other hand, the geometric characteristics of directional interactions and shape fit, which play an important role in chiral recog... (English)
9 February 2022
0 references
Budapest, Budapest
0 references
Identifiers
VEKOP-2.3.3-15-2017-00018
0 references