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4AWJ

pVHL:EloB:EloC complex, in complex with capped Hydroxyproline

Summary for 4AWJ
Entry DOI10.2210/pdb4awj/pdb
Related1LM8 1LQB 1VCB 2C9W 2IZV 2XAI 3ZRC 3ZRF 3ZTC 3ZTD 3ZUN 4AJY
DescriptorTRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 2, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, VON HIPPEL-LINDAU DISEASE TUMOR SUPPRESSOR, ... (8 entities in total)
Functional Keywordstranscription, e3 ubiquitin ligase, tumor supressor
Biological sourceHOMO SAPIENS (HUMAN)
More
Cellular locationNucleus (Probable): Q15370 Q15369
Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337
Total number of polymer chains12
Total formula weight168752.87
Authors
Van Molle, I.,Thomann, A.,Buckley, D.L.,So, E.C.,Lang, S.,Crews, C.M.,Ciulli, A. (deposition date: 2012-06-04, release date: 2012-11-14)
Primary citationVan Molle, I.,Thomann, A.,Buckley, D.L.,So, E.C.,Lang, S.,Crews, C.M.,Ciulli, A.
Dissecting Fragment-Based Lead Discovery at the Von Hippel-Lindau Protein:Hypoxia Inducible Factor 1Alpha Protein-Protein Interface.
Chem.Biol., 19:1300-, 2012
Cited by
PubMed Abstract: Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1α interaction into their component fragments. Using biophysical techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed.
PubMed: 23102223
DOI: 10.1016/J.CHEMBIOL.2012.08.015
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.5 Å)
Structure validation

226707

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