3LVP

Crystal structure of bisphosphorylated IGF1-R Kinase domain (2P) in complex with a bis-azaindole inhibitor

PDB DOI: https://doi.org/10.2210/pdb3LVP/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2010-02-22 Released: 2010-07-21
Deposition Author(s): Maignan, S., Marquette, J.P., Guilloteau, J.P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.279
R-Value Work: 0.226

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Design of Potent IGF1-R Inhibitors Related to Bis-azaindoles

Nemecek, C., Metz, W.A., Wentzler, S., Ding, F.X., Venot, C., Souaille, C., Dagallier, A., Maignan, S., Guilloteau, J.P., Bernard, F., Henry, A., Grapinet, S., Lesuisse, D.

(2010) Chem Biol Drug Des 76: 100-106

PubMed: 20545947 Search on PubMed
DOI: https://doi.org/10.1111/j.1747-0285.2010.00991.x
Primary Citation of Related Structures:
3LVP

PubMed Abstract:
From an azaindole lead, identified in high throughput screen, a series of potent bis-azaindole inhibitors of IGF1-R have been synthesized using rational drug design and SAR based on a in silico binding mode hypothesis. Although the resulting compounds produced the expected improved potency, the model was not validated by the co-crystallization experiments with IGF1-R.

Organizational Affiliation

Medicinal Chemistry, Sanofi-Aventis, 13 Quai Jules Guesde, 94300 Vitry-sur-Seine, France.

Macromolecule Content

Total Structure Weight: 155.68 kDa
Atom Count: 9,405
Modelled Residue Count: 1,159
Deposited Residue Count: 1,344
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Insulin-like growth factor 1 receptor	A, B, C, D	336	Homo sapiens	Mutation(s): 0 Gene Names: IGF1R EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P08069 (Homo sapiens) Explore P08069 Go to UniProtKB: P08069
PHAROS: P08069 GTEx: ENSG00000140443
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08069
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
PDR Query on PDR Download Ideal Coordinates CCD File SDF format, chain J [auth C] SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain K [auth D] MOL2 format, chain J [auth C] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain K [auth D]	E [auth A], H [auth B], J [auth C], K [auth D]	3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-2-yl)-5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridine C₁₇ H₁₅ Cl N₄ O₂ ISLVGFDZMORPFI-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth D]
EPE Query on EPE Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A]	F [auth A]	4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID C₈ H₁₈ N₂ O₄ S JKMHFZQWWAIEOD-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain I [auth B] MOL2 format, chain G [auth A] MOL2 format, chain I [auth B]	G [auth A], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain G [auth A] Focus chain I [auth B] Interactions & Density Focus chain G [auth A] Focus chain I [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
PDR	PDBBind: 3LVP	IC50: 2 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.279
R-Value Work: 0.226
Space Group: P 4₃ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 94.95	α = 90
b = 94.95	β = 90
c = 322.29	γ = 90

Software Package:

Software Name	Purpose
AMoRE	phasing
CNS	refinement
DENZO	data reduction
SCALEPACK	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-07-21

Deposition Author(s):

Maignan, S.

Marquette, J.P.

Guilloteau, J.P.

Revision History (Full details and data files)

Version 1.0: 2010-07-21
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2023-11-01
Changes: Data collection, Database references, Derived calculations, Refinement description

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Help and Resources

3LVP

Crystal structure of bisphosphorylated IGF1-R Kinase domain (2P) in complex with a bis-azaindole inhibitor

Design of Potent IGF1-R Inhibitors Related to Bis-azaindoles

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)