The Evolving Role of Structural Biology in Drug Discovery

Renaud, Jean‐Paul

doi:10.1002/9781118681121.ch1

Cited by 5 publications

(4 citation statements)

References 231 publications

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“…Currently, this strategy depends not only on structural information, but also on dynamics, kinetics, and enzyme-substrate interaction data, that together provide the dynamic information on protein's in vitro conformation and flexibility and are possible due to the computational advances that emerged over years. (25,26) Some studies have used GS enzymes as a therapeutic target to treat diseases such as cancer, malaria, and leishmaniases. (23,24,27,28) The LbGS lacks structural and functional studies being the studies with GS from L. donovani (LdGS) the closest to LbGS.…”

Section: Resultsmentioning

confidence: 99%

Cross-linking mass spectrometry reveals structural insights of the glutamine synthetase from Leishmania braziliensis

Lima

Santos

Murakami

et al. 2021

Mem. Inst. Oswaldo Cruz

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BACKGROUND Leishmaniasis is a neglected tropical disease caused by the parasite Leishmania braziliensis, commonly found in Brazil and associated with cutaneous and visceral forms of this disease. Like other organisms, L. braziliensis has an enzyme called glutamine synthetase (LbGS) that acts on the synthesis of glutamine from glutamate. This enzyme plays an essential role in the metabolism of these parasites and can be a potential therapeutic target for treating this disease.OBJECTIVES Investigate LbGS structure and generate structural models of the protein.METHODS We use the method of crosslinking mass spectrometry (XLMS) and generate structural models in silico using I-TASSER.FINDINGS 42 XLs peptides were identified, of which 37 are explained in a monomeric model with the other five indicating LbGS dimerization and pentamers interaction region. The comparison of 3D models generated in the presence and absence of XLMS restrictions probed the benefits of modeling with XLMS highlighting the inappropriate folding due to the absence of spatial restrictions. MAIN CONCLUSIONSIn conclusion, we disclose the conservation of the active site and interface regions, but also unique features of LbGS showing the potential of XLMS to probe structural information and explore new drugs.

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Section: Resultsmentioning

confidence: 99%

Cross-linking mass spectrometry reveals structural insights of the glutamine synthetase from Leishmania braziliensis

Lima

Santos

Murakami

et al. 2021

Mem. Inst. Oswaldo Cruz

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“…The state-of-the-art of drug discovery pipelines in traditional macromolecular crystallography is constantly evolving and improving. High-throughput ligand investigations by streamlined soaking or injecting experiments that are aided by robotics are currently capable of screening hundreds of large crystals a day (Renaud, 2020). The on-grid method presented here soaks thousands of crystals at once, uses only 1-3 mL of the soaking solution, requires no manual manipulation of the individual crystals, and does not require a cryo-protective back soak, since crystals vitrified using supercooled ethane typically show no solvent rings (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Ligand Incorporation into Protein Microcrystals for MicroED by On-Grid Soaking

Martynowycz

Gonen

2021

Structure

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“…structure-based drug discovery, SBDD). W rezultacie zaprojektowane leki są dobrze dopasowane do celu terapeutycznego (wysoce specyficzne), co przyczynia się do zwiększenia ich skuteczności i ograniczenia skutków ubocznych [39].…”

Section: Zastosowanie Biologii Strukturalnej W Projektowaniu Lekówunclassified

Postępy biologii strukturalnej – jak zobaczyć cząsteczki życia?

Witek,

Ragin,

Tran

et al. 2024

Postepy Biochem

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Structural biology is focused on understanding the architecture of biomolecules, such as proteins and nucleic acids. Deciphering the structure helps to understand their function in the cell at a very precise – molecular level. This makes it possible to not only determine the basis of diseases but also to propose therapeutic strategies and tools. Such a strong motivation for the development of structural biology has led to the development of a number of methods, which enable determination of the structures of the molecules of life. The continuous progress has been enabled by the integration of biology, chemistry, physics, and computer science, making structural biology extremely interdisciplinary. In its 35-year history, the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan has become one of the key Polish institutions conducting research in the field of structural biology. On one hand, the research has brought international recognition, and on the other hand, it has forced the implementation and development of cutting-edge methods. This review discusses the methods used in structural biology at the Institute.

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The Evolving Role of Structural Biology in Drug Discovery

Cited by 5 publications

References 231 publications

Cross-linking mass spectrometry reveals structural insights of the glutamine synthetase from Leishmania braziliensis

Cross-linking mass spectrometry reveals structural insights of the glutamine synthetase from Leishmania braziliensis

Ligand Incorporation into Protein Microcrystals for MicroED by On-Grid Soaking

Postępy biologii strukturalnej – jak zobaczyć cząsteczki życia?

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