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PDBsum entry 4wqo
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Transcription
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PDB id
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4wqo
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Contents |
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148 a.a.
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104 a.a.
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96 a.a.
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141 a.a.
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PDB id:
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Transcription
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Title:
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Structure of vhl-elob-eloc-cul2
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Structure:
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Von hippel-lindau disease tumor suppressor. Chain: a. Synonym: protein g7,pvhl. Engineered: yes. Transcription elongation factor b polypeptide 2. Chain: b. Synonym: elongin 18 kda subunit,elongin-b,elob,RNA polymerase ii transcription factor siii subunit b,siii p18. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: vhl. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: tceb2. Gene: tceb1. Gene: cul2.
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Resolution:
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3.20Å
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R-factor:
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0.222
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R-free:
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0.250
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Authors:
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H.C.Nguyen,Y.Xiong
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Key ref:
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H.C.Nguyen
et al.
(2015).
Insights into Cullin-RING E3 ubiquitin ligase recruitment: structure of the VHL-EloBC-Cul2 complex.
Structure,
23,
441-449.
PubMed id:
DOI:
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Date:
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22-Oct-14
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Release date:
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04-Mar-15
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PROCHECK
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Headers
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References
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P40337
(VHL_HUMAN) -
von Hippel-Lindau disease tumor suppressor from Homo sapiens
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Seq:
Struc:
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213 a.a.
148 a.a.
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Q15370
(ELOB_HUMAN) -
Elongin-B from Homo sapiens
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Seq:
Struc:
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118 a.a.
104 a.a.
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DOI no:
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Structure
23:441-449
(2015)
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PubMed id:
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Insights into Cullin-RING E3 ubiquitin ligase recruitment: structure of the VHL-EloBC-Cul2 complex.
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H.C.Nguyen,
H.Yang,
J.L.Fribourgh,
L.S.Wolfe,
Y.Xiong.
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ABSTRACT
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The von Hippel-Lindau tumor suppressor protein (VHL) recruits a Cullin 2 (Cul2)
E3 ubiquitin ligase to downregulate HIF-1α, an essential transcription factor
for the hypoxia response. Mutations in VHL lead to VHL disease and renal cell
carcinomas. Inhibition of this pathway to upregulate erythropoietin production
is a promising new therapy to treat ischemia and chronic anemia. Here, we report
the crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and
Elongin C (EloC). Cul2 interacts with both the VHL BC box and cullin box and a
novel EloC site. Comparison with other cullin E3 ligase structures shows that
there is a conserved, yet flexible, cullin recognition module and that cullin
selectivity is influenced by distinct electrostatic interactions. Our structure
provides a structural basis for the study of the pathogenesis of VHL disease and
rationale for the design of novel compounds that may modulate cullin-substrate
receptor interactions.
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