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News

1 Mar 2021

Emerging Topics in Biomolecular Magnetic Resonance - Birthe Kragelund (University of Copenhagen) and Ulrich Günther (University of Lübeck)

The series Emerging topics in Biomolecular Magnetic Resonance will continue on March 4^th at 16:00 CEST with the following lecturers and topics:

Birthe Kragelund (University of Copenhagen): Disordered complexes involving highly charged proteins
Ulrich Günther (University of Lübeck): New Insights in COVID-19 from NMR Metabolomics

25 Feb 2021

Instruct-ERIC CZ webinar recording

You can now play the recording of Instruct-ERIC webinar hosted by Czech Infrastructure for Integrative Structural Biology (CIISB) with presentations of Pavel Plevka, Jan Dohnálek, and Lukáš Trantírek.

22 Feb 2021

Upgrades at X-ray Diffraction and Bio-SAXS Core Facility

The universal, dual wavelength (Mo-Kα and Cu-Kα) diffractometer operated by X-ray Diffraction and Bio-SAXS Core Facility has been upgraded from the configuration Rigaku HighFlux HomeLab to the configuration Rigaku XtaLAB Synergy-DW™. The old X-ray detector Saturn 724+ based on CCD sensor Kodak KAF-4320E was replaced by a modern HPC (Hybrid Photon Counting) detector HyPix-6000HE and the old partial-chi axis goniometer AFC-11 by a fast high-precision 4-circle kappa goniometer. The effective performance of the diffractometer has increased approx 4 times, the new system is able to collect a complete diffraction datasets within a few (=1-3) hours, and the maximum resolution of diffraction data achievable before and after this upgrade has increased by about 0.3-0.5 Å.

22 Feb 2021

Emerging Topics in Biomolecular Magnetic Resonance - Lucio Frydman (Weizmann Institute) and Mike Williamson (University of Sheffield)

The series Emerging topics in Biomolecular Magnetic Resonance will continue on February 25^th at 16:00 CEST with the following lecturers and topics:

Lucio Frydman (Weizmann Institute): Putting annoying chemical exchanges to good use in the solution-state NMR of sugars, proteins and nucleic acids
Mike Williamson (University of Sheffield): Measuring the accuracy of NMR protein structures

15 Feb 2021

Emerging Topics in Biomolecular Magnetic Resonance - Roland Riek (ETH Zürich) and Patrick van der Wel (University of Groningen)

The series Emerging topics in Biomolecular Magnetic Resonance will continue on February 18^th at 16:00 CEST with the following lecturers and topics:

Roland Riek (ETH Zürich): On automated structure and multi-state structure determination by NMR
Patrick van der Wel (University of Groningen): SSNMR-detected mobility in substrate-mediated protein activation

11 Feb 2021

Upgrades in the Josef Dadok National NMR Centre in 2020

In the period of 2020 to 2022, the spectrometers in the Josef Dadok National NMR Centre are undergoing thorough upgrades. In late 2020, the electronics of the instruments was replaced by the latest Bruker technology AVANCE NEO. The only difference visible from the outside is that the electronics cabinets are now smaller, half the previous size. And from the functionality point of view, there are improvements in flexibility and stability. The AVANCE NEO is based on a ‘transceive’ principle, meaning each NMR channel has both transmit and receive capabilities.

In 2021, the upgrades will continue by acquiring new probes.

Highlights of Coronavirus Structural Studies

15 May 2020

Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading around the world. There is no existing vaccine or proven drug to pre- vent infections and stop virus proliferation. Although this virus is similar to human and animal SARS-CoVs and Middle East Respiratory Syndrome coronavirus (MERS-CoVs), the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. Andrzej Joachimiak et. al applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases, Argonne National Laboratory, to produce SARS-CoV-2 proteins and structures. In the Protein Science paper they report two high-resolution crystal structures of endoribonuclease Nsp15/NendoU and compare these structures with previously reported homologs from SARS and MERS coronaviruses.

5 May 2020

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome– coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. The Science article by Qiang Zhou et. al. presents cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain
of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.

5 May 2020

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome– coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (Mpro, also called 3CLpro) because of its essential role in processing the polyproteins that are translated from the viral RNA. Rolf Hingenfeld et. al. report in Science the x-ray structures of the unliganded SARS-CoV-2 Mpro and its complex with an a-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, they developed the lead compound into a potent inhibitor of the SARS-CoV-2 Mpro. The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.

Newsletters

Reader's Corner Archive

Visualization of biological macromolecules at near-atomic resolution: cryo-electron microscopy comes of age

The topical review by Alok K. Mitra recapitulates developments and transformational advances of cryo-EM technology.

16 Jul 2019

The expanding toolkit for structural biology: synchrotrons, X-ray lasers and cryo-EM

Samar Hasnain et. al. describe the steadily-expanding methodologies for atomic resolution studies in The expanding toolkit for structural biology: synchrotrons, X-ray lasers and cryo-EM. Of note is the following statistics: Despite the wealth of structures in the Protein Data Bank, a closer examination reveals that 89% of the structures, i.e. 126 994, are of proteins or complexes with a molecular weight of less than 160 kDa. Furthermore, only 4% of the deposited structures have a molecular weight in excess of 300 kDa.