PDBsum entry 3ztc

Transcription

PDB id: 3ztc

Contents

Protein chains

103 a.a.

86 a.a.

141 a.a.

87 a.a.

Ligands

TR0 ×4

Waters ×73

PDB id:

3ztc

Name:

Transcription

Title:

Pvhl54-213-elob-eloc complex _ (2s,4r)-n-((1,1'-biphenyl)-4-ylmethyl)- 4-hydroxy-1-(2-(3-methylisoxazol-5-yl)acetyl)pyrrolidine-2- carboxamide

Structure:

Transcription elongation factor b polypeptide 2. Chain: a, d, g, j. Synonym: elongin 18 kda subunit, elongin-b, elob, RNA polymerase ii transcription factor siii subunit b, siii p18, elonginb. Engineered: yes. Transcription elongation factor b polypeptide 1. Chain: b, e, h, k. Synonym: elongin 15 kda subunit, elongin-c, eloc, RNA polymerase ii transcription factor siii subunit c, siii p15, elonginc.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.65Å R-factor: 0.243 R-free: 0.317

Authors:

I.Van Molle,D.L.Buckley,C.M.Crews,A.Ciulli

Key ref:

I.Van Molle et al. (2012). Dissecting fragment-based lead discovery at the von Hippel-Lindau protein:hypoxia inducible factor 1α protein-protein interface. Chem Biol, 19, 1300-1312. PubMed id: 23102223

Date:

06-Jul-11 Release date: 25-Jul-12

Protein chains

Q15370  (ELOB_HUMAN) -  Elongin-B from Homo sapiens

Seq: 118 a.a.

Struc: 103 a.a.

Protein chain

Q15369  (ELOC_HUMAN) -  Elongin-C from Homo sapiens

Seq: 112 a.a.

Struc: 86 a.a.

Protein chains

P40337  (VHL_HUMAN) -  von Hippel-Lindau disease tumor suppressor from Homo sapiens

Seq: 213 a.a.

Struc: 141 a.a.

Protein chains

Q15369  (ELOC_HUMAN) -  Elongin-C from Homo sapiens

Seq: 112 a.a.

Struc: 87 a.a.

Chem Biol 19:1300-1312 (2012)

PubMed id: 23102223

Dissecting fragment-based lead discovery at the von Hippel-Lindau protein:hypoxia inducible factor 1α protein-protein interface.

I.Van Molle, A.Thomann, D.L.Buckley, E.C.So, S.Lang, C.M.Crews, A.Ciulli.

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.