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. 2021 Sep 15;26(18):5606. doi: 10.3390/molecules26185606

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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CRL2^VHL (a) Schematic representation of the assembly of the CRL2^VHL E3 ligase: ubiquitin (Ub) in purple, E2 ligase (E2) in dark blue, Ring Box Protein 1 (Rbx1) in yellow, Cullin-2 (Cul2) in magenta, adaptor protein Elongin B (EloB) in orange and Elongin C (EloC) in green, substrate recognition protein VHL (VHL) in light blue, and substrate protein in grey. Protein assembly I is the 3D representation of the system made up of Cul2, EloB, EloC, and a small α-helix of VHL as found in PDB code 5N4W. Protein assembly II is the 3D representation of the N-terminal end of Cul2 bound to EloB, EloC, and VHL, as found in PDB code 4WQO. (b) 2D representation of the structures of the main VHL:HIF-1α inhibitors developed by Ciulli A. et al. [63,64]. The hydroxylated proline that mimics the activated HIF-1 α is represented in blue.

CRL2^VHL (a) Schematic representation of the assembly of the CRL2^VHL E3 ligase: ubiquitin (Ub) in purple, E2 ligase (E2) in dark blue, Ring Box Protein 1 (Rbx1) in yellow, Cullin-2 (Cul2) in magenta, adaptor protein Elongin B (EloB) in orange and Elongin C (EloC) in green, substrate recognition protein VHL (VHL) in light blue, and substrate protein in grey. Protein assembly I is the 3D representation of the system made up of Cul2, EloB, EloC, and a small α-helix of VHL as found in PDB code 5N4W. Protein assembly II is the 3D representation of the N-terminal end of Cul2 bound to EloB, EloC, and VHL, as found in PDB code 4WQO. (b) 2D representation of the structures of the main VHL:HIF-1α inhibitors developed by Ciulli A. et al. [63,64]. The hydroxylated proline that mimics the activated HIF-1 α is represented in blue.