2PE2 | pdb_00002pe2

CRYSTAL STRUCTURE OF HUMAN PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1 (PDK1) 3-{5-[2-Oxo-5-ureido-1,2-dihydro-indol-(3Z)-ylidenemethyl]-1H-pyrrol-3-yl}-N-(2-piperidin-1-yl-ethyl)-benzamide COMPLEX

PDB DOI: https://doi.org/10.2210/pdb2PE2/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: unidentified baculovirus
Mutation(s): Yes

Deposited: 2007-04-01 Released: 2007-06-19
Deposition Author(s): Whitlow, M., Adler, M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.13 Å
R-Value Free:
0.215 (Depositor), 0.216 (DCC)
R-Value Work:
0.188 (Depositor), 0.197 (DCC)
R-Value Observed:
0.189 (Depositor)

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: Optimization of BX-517.

Islam, I., Brown, G., Bryant, J., Hrvatin, P., Kochanny, M.J., Phillips, G.B., Yuan, S., Adler, M., Whitlow, M., Lentz, D., Polokoff, M.A., Wu, J., Shen, J., Walters, J., Ho, E., Subramanyam, B., Zhu, D., Feldman, R.I., Arnaiz, D.O.

(2007) Bioorg Med Chem Lett 17: 3819-3825

PubMed: 17544272 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2007.05.060
Primary Citation of Related Structures:
2PE2

PubMed Abstract:
Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.

Organizational Affiliation

Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA. imadulislam@yahoo.com

Macromolecule Content

Total Structure Weight: 34.65 kDa
Atom Count: 2,516
Modelled Residue Count: 276
Deposited Residue Count: 286
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
3-phosphoinositide-dependent protein kinase 1	A	286	Homo sapiens	Mutation(s): 1 Gene Names: PDPK1, PDK1 EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O15530 (Homo sapiens) Explore O15530 Go to UniProtKB: O15530
PHAROS: O15530 GTEx: ENSG00000140992
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O15530
Sequence Annotations Expand
Reference Sequence LOADING

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
464 Query on 464 Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	3-[5-({5-[(AMINOCARBONYL)AMINO]-2-OXO-2H-INDOL-3-YL}METHYL)-1H-PYRROL-3-YL]-N-(2-PIPERIDIN-1-YLETHYL)BENZAMIDE C₂₈ H₃₀ N₆ O₃ PWZOBKJHPWISGC-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] SDF format, chain C [auth A] SDF format, chain D [auth A] MOL2 format, chain B [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] mmCIF format, chain B [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A]	B [auth A], C [auth A], D [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain B [auth A] Focus chain C [auth A] Focus chain D [auth A] Interactions & Density Focus chain B [auth A] Focus chain C [auth A] Focus chain D [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A]	F [auth A] G [auth A] H [auth A] I [auth A] J [auth A] F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
SEP Query on SEP	A	L-PEPTIDE LINKING	C₃ H₈ N O₆ P		SER

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.13 Å
R-Value Free: 0.215 (Depositor), 0.216 (DCC)
R-Value Work: 0.188 (Depositor), 0.197 (DCC)
R-Value Observed: 0.189 (Depositor)

Space Group: P 3₂ 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 123.223	α = 90
b = 123.223	β = 90
c = 47.386	γ = 120

Software Package:

Software Name	Purpose
CNX	refinement
XTALVIEW	refinement
X-GEN	data reduction
X-GEN	data scaling
X-PLOR	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2007-06-19

Deposition Author(s):

Whitlow, M.

Adler, M.

Revision History (Full details and data files)

Version 1.0: 2007-06-19
Type: Initial release
Version 1.1: 2008-05-01
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Derived calculations, Version format compliance
Version 1.3: 2024-11-20
Changes: Data collection, Database references, Derived calculations, Structure summary

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Deposit Data

Help and Resources

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CRYSTAL STRUCTURE OF HUMAN PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1 (PDK1) 3-{5-[2-Oxo-5-ureido-1,2-dihydro-indol-(3Z)-ylidenemethyl]-1H-pyrrol-3-yl}-N-(2-piperidin-1-yl-ethyl)-benzamide COMPLEX

Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: Optimization of BX-517.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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