The XFEL Protein Crystallography: Developments and Perspectives

Liu, Haiguang; Lee, Weontae

doi:10.3390/ijms20143421

Cited by 16 publications

(15 citation statements)

References 36 publications

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“…Over the past ten years, we have witnessed the development of X-ray-free electron lasers (XFELs) and their applications in many scientific fields, primarily protein crystallography [84]. The peak brightness obtained with such sources is 10 billion times higher than that obtained with third generation synchrotrons.…”

Section: Discussion-comparison With Other Methods: Serial Crystallogrmentioning

confidence: 99%

Protein X-ray Crystallography and Drug Discovery

2020

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With the advent of structural biology in the drug discovery process, medicinal chemists gained the opportunity to use detailed structural information in order to progress screening hits into leads or drug candidates. X-ray crystallography has proven to be an invaluable tool in this respect, as it is able to provide exquisitely comprehensive structural information about the interaction of a ligand with a pharmacological target. As fragment-based drug discovery emerged in the recent years, X-ray crystallography has also become a powerful screening technology, able to provide structural information on complexes involving low-molecular weight compounds, despite weak binding affinities. Given the low numbers of compounds needed in a fragment library, compared to the hundreds of thousand usually present in drug-like compound libraries, it now becomes feasible to screen a whole fragment library using X-ray crystallography, providing a wealth of structural details that will fuel the fragment to drug process. Here, we review theoretical and practical aspects as well as the pros and cons of using X-ray crystallography in the drug discovery process.

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Section: Discussion-comparison With Other Methods: Serial Crystallogrmentioning

confidence: 99%

Protein X-ray Crystallography and Drug Discovery

2020

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“…A new technique for crystal structure resolution has recently been developed, X-ray-free electron laser (XFEL) crystallography. The use of lasers reduces the size of the crystals required and, therefore, increases their stability [314,315].…”

Section: B Novel Structures and Drug Design Approachesmentioning

confidence: 99%

Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

Raymond¹,

Aktary²,

Larue³

et al. 2022

Preprint

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G protein-coupled receptors (GPCRs) serve prominent roles in melanocyte lineage physiology, with an impact at all stages of development, as well as on mature melanocyte functions. GPCR ligands are present in the skin and regulate melanocyte homeostasis, including pigmentation. The role of GPCRs in the regulation of pigmentation and, consequently, protection against external aggression, such as ultraviolet radiation, has long been established. However, evidence of new functions of GPCRs directly in melanomagenesis has been highlighted in recent years. GPCRs are coupled, through their intracellular domains, to heterotrimeric G proteins, which induce cellular signaling through various pathways. Such signaling modulates essential cellular processes of melanomagenesis, such as proliferation and migration. GPCR-associated signaling in melanoma can be activated by the binding of paracrine factors to their receptors or directly by activating mutations. In this review, we present melanoma-associated alterations of GPCRs and their downstream signaling and discuss the various preclinical models used to evaluate new therapeutic approaches against GPCR activity in melanoma. Recent striking advances in our understanding of the structure, function, and regulation of GPCRs will undoubtedly broaden treatment options in melanoma in the future.

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“…X-ray free electron lasers in the hard X-ray range significantly change the experimental procedure involving time resolved femtosecond crystallography [128] for biological objects. Any XFEL approach to the crystallographic study of proteins includes four main stages [129]: (i) portion preparation of microcrystal samples, (ii) delivery and manipulation of samples, (iii) operation of an XFEL and an instrument for the acquisition of diffraction data, and (iv) analysis of data and interpretation of models. One of the actively used methods is time-resolved X-ray scattering in solutions (TR-XSS) [130].…”

Section: Biological Objectsmentioning

confidence: 99%

Diagnostics of Nanosystems with the Use of Ultrashort X-Ray Pulses: Theory and Experiment (Brief Review)

2021

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X-ray diffraction analysis is one of the famous widely used methods to study the structure of matter. It is well known that the scattering of ultrashort X-ray pulses can be used in X-ray diffraction analysis. The scattering of such pulses by various multiatomic objects and nanosystems leads to diffraction patterns carrying information not only on the structure of an object but also on the dynamics of processes in this object. Currently, it is technically possible to fabricate intense sources of femto-and attosecond pulses. New theories including the specificity of the interaction of such pulses with matter are not necessarily applied in the X-ray diffraction analysis involving ultrashort pulses. The inclusion of this specificity should lead to a better use of capabilities of sources of ultrashort pulses and to new scientific results. Sources of X-ray ultrashort pulses, widely used methods and new theories of the X-ray diffraction analysis including the specificity of the interaction of such pulses with matter, and modern experiments involving ultrashort pulses are briefly reviewed here.

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The XFEL Protein Crystallography: Developments and Perspectives

Abstract: In the past 10 years, the world has witnessed the revolutionary development of X-ray free electron lasers (XFELs) and their applications in many scientific disciplinaries [...]

Cited by 16 publications

References 36 publications

Protein X-ray Crystallography and Drug Discovery

Protein X-ray Crystallography and Drug Discovery

Targeting GPCRs & their Signaling as a Therapeutic Option in Melanoma

Diagnostics of Nanosystems with the Use of Ultrashort X-Ray Pulses: Theory and Experiment (Brief Review)

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