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Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme

Ubiquitin and ubiquitin-like modifiers such as SUMO play important roles in several cellular pathways that can become deregulated in cancer. Here the authors describe the structural basis for inhibition of SUMO E1 ligase by the small molecule COH000.

Zongyang Lv
Lingmin Yuan
Shaun K. Olsen
ResearchOpen Access04 Dec 2018
Nature Communications

Volume: 9, P: 1-12
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
Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI

HHARI is a RING-in-between-RING (RBR) ubiquitin (Ub) E3 ligase. Here the authors present the crystal structure of HHARI with the UbcH7 ~ Ub thioester intermediate mimetic, which reveals that HHARI binds this E2 ~ Ub in an open conformation and explains the specificity of this cognate RBR E3/E2 pair.

Lingmin Yuan
Zongyang Lv
Shaun K. Olsen
ResearchOpen Access08 Aug 2017
Nature Communications

Volume: 8, 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
Crystal structures of an E1–E2–ubiquitin thioester mimetic reveal molecular mechanisms of transthioesterification

The molecular mechanism of ubiquitin transfer from E1 to E2 enzymes is still unclear. By solving the crystal structure of a covalently trapped E1–E2–ubiquitin thioester mimetic, the authors identify two conformations of this complex which suggest an affinity switch mechanism for thioester transfer.

Lingmin Yuan
Zongyang Lv
Shaun K. Olsen
ResearchOpen Access22 Apr 2021
Nature Communications

Volume: 12, P: 1-13
Crystal structure of an avian influenza polymerase PA_N reveals an endonuclease active site

This paper reports the crystal structure of the amino terminus of the PA subunit of the influenza RNA polymerase, and provides evidence that it has endonuclease activity.

Puwei Yuan
Mark Bartlam
Yingfang Liu
Research04 Feb 2009
Nature

Volume: 458, P: 909-913
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
Crystal structure and nucleotide selectivity of human IFIT5/ISG58

Feng Feng
Lingmin Yuan
Huanhuan Liang
Correspondence18 Jun 2013
Cell Research

Volume: 23, P: 1055-1058

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