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Cryo-EM structures reveal the molecular mechanism of SUMO E1–E2 thioester transfer

This study reveals how human small ubiquitin-like modifier (SUMO) E1 recruits its E2 partner UBC9 and transfers SUMO1 through large structural changes, uncovering key mechanisms that ensure specificity and fidelity in SUMOylation, an essential protein modification pathway.

Anindita Nayak
Digant Nayak
Shaun K. Olsen
ResearchOpen Access25 Sept 2025
Nature Structural & Molecular Biology

Volume: 32, P: 2441-2453
Development and crystal structures of a potent second-generation dual degrader of BCL-2 and BCL-xL

Here, the authors have determined structures of 753b PROTAC, BCL-xL/BCL-2 and VHL E3 ligase ternary complexes which reveal the basis for the dual degrader activity of 753b. The structures and subsequent functional analyses facilitated design of WH244 PROTAC, with enhanced degrader activity in cells.

Digant Nayak
Dongwen Lv
Shaun K. Olsen
ResearchOpen Access29 Mar 2024
Nature Communications

Volume: 15, P: 1-17
Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer

ISGylation plays a crucial role in the innate immune response and requires sequential activity of E1, E2, and E3 enzymes. Here, the authors present cyro-EM structures that reveal the molecular mechanisms underlying ISG15 activation by the E1 enzyme Uba7 and transfer to its cognate E2 enzyme UBE2L6.

Mohammad Afsar
GuanQun Liu
Shaun K. Olsen
ResearchOpen Access08 Aug 2023
Nature Communications

Volume: 14, P: 1-14
Crystal structures reveal catalytic and regulatory mechanisms of the dual-specificity ubiquitin/FAT10 E1 enzyme Uba6

Uba6 is an E1 enzyme that regulates numerous cellular processes by activating ubiquitin and FAT10 pathways. Here, the authors present crystal structures that illuminate Uba6 catalytic mechanisms and reveal inositol hexakisphosphate as a cofactor that modulates Uba6 activity.

Lingmin Yuan
Fei Gao
Shaun K. Olsen
ResearchOpen Access19 Aug 2022
Nature Communications

Volume: 13, P: 1-14
Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity,

Simultaneous targeting of BCL-xL and BCL-2 is an attractive approach for cancer treatment. Based on information gained by computational structure modelling, the authors develop a PROTAC that induces degradation of both BCL-xL and BCL-2 and effectively targets BCL-xL/2-dependent leukaemia cells.

Dongwen Lv
Pratik Pal
Daohong Zhou
ResearchOpen Access25 Nov 2021
Nature Communications

Volume: 12, P: 1-14
Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PL^pro and M^pro proteases, and nsp14 guanine N7-methyltransferase

Mikolaj Zmudzinski
Wioletta Rut
Marcin Drag
ResearchOpen Access06 Jun 2023
Scientific Reports

Volume: 13, P: 1-16
Evaluation of the anti-SARS-CoV-2 properties of essential oils and aromatic extracts

Daniel Jan Strub
Michał Talma
Marcin Drąg
ResearchOpen Access20 Aug 2022
Scientific Reports

Volume: 12, P: 1-14

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Cryo-EM structures reveal the molecular mechanism of SUMO E1–E2 thioester transfer

Development and crystal structures of a potent second-generation dual degrader of BCL-2 and BCL-xL

Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer

Crystal structures reveal catalytic and regulatory mechanisms of the dual-specificity ubiquitin/FAT10 E1 enzyme Uba6

Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity,

Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PLpro and Mpro proteases, and nsp14 guanine N7-methyltransferase

Evaluation of the anti-SARS-CoV-2 properties of essential oils and aromatic extracts

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Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PL^pro and M^pro proteases, and nsp14 guanine N7-methyltransferase