4b9k

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pVHL-ELOB-ELOC complex_(2S,4R)-1-(3-amino-2-methylbenzoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide bound

Structural highlights

4b9k is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:ACT, CAS, TG0
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ELOC_HUMAN SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).[1] The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.[2]

Publication Abstract from PubMed

By design: Novel small-molecule inhibitors of the interaction between the von Hippel-Lindau ligase (VHL) and its molecular target HIF1alpha, a transcription factor involved in oxygen sensing, have been developed and studied. The most potent inhibitor binds with an IC(50) value of 0.9 microM and is thus the first sub-micromolar inhibitor of the VHL-HIF1alpha interaction.

Small-Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1alpha,Buckley DL, Gustafson JL, Van Molle I, Roth AG, Tae HS, Gareiss PC, Jorgensen WL, Ciulli A, Crews CM Angew Chem Int Ed Engl. 2012 Oct 12. doi: 10.1002/anie.201206231. PMID:23065727[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
  2. ↑ Kario E, Marmor MD, Adamsky K, Citri A, Amit I, Amariglio N, Rechavi G, Yarden Y. Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling. J Biol Chem. 2005 Feb 25;280(8):7038-48. Epub 2004 Dec 7. PMID:15590694 doi:10.1074/jbc.M408575200
  3. ↑ Buckley DL, Gustafson JL, Van Molle I, Roth AG, Tae HS, Gareiss PC, Jorgensen WL, Ciulli A, Crews CM. Small-Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1alpha Angew Chem Int Ed Engl. 2012 Oct 12. doi: 10.1002/anie.201206231. PMID:23065727 doi:http://dx.doi.org/10.1002/anie.201206231

Contents


PDB ID 4b9k

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OCA

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