2ZB2

Human liver glycogen phosphorylase a complexed with glcose and 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide

PDB DOI: https://doi.org/10.2210/pdb2ZB2/pdb

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

Deposited: 2007-10-15 Released: 2008-09-02
Deposition Author(s): Katayama, N., Onda, K.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.45 Å
R-Value Free: 0.307
R-Value Work: 0.261
R-Value Observed: 0.300

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

This is version 1.4 of the entry. See complete history.

Literature

Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a.

Onda, K., Suzuki, T., Shiraki, R., Yonetoku, Y., Negoro, K., Momose, K., Katayama, N., Orita, M., Yamaguchi, T., Ohta, M., Tsukamoto, S.

(2008) Bioorg Med Chem 16: 5452-5464

PubMed: 18434170 Search on PubMed
DOI: https://doi.org/10.1016/j.bmc.2008.04.010
Primary Citation of Related Structures:
2ZB2

PubMed Abstract:
A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f showed inhibitory activity of glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) of 0.62microM and oral hypoglycemic activity in diabetic db/db mice. Crystallographic determination of the complex of 2f with hLGPa showed binding of the inhibitor in a solvent cavity at the dimer interface, with the two hydroxyl groups making favorable electrostatic interactions with hLGPa.

Organizational Affiliation

Drug Discovery Research, Astellas Pharma Inc., 5-2-3 Toukoudai, Tsukuba, Ibaraki 300-2698, Japan. [email protected]

Macromolecule Content

Total Structure Weight: 196.98 kDa
Atom Count: 13,413
Modelled Residue Count: 1,589
Deposited Residue Count: 1,698
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Glycogen phosphorylase, liver form	A, B	849	Homo sapiens	Mutation(s): 0 Gene Names: PYGL EC: 2.4.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P06737 (Homo sapiens) Explore P06737 Go to UniProtKB: P06737
PHAROS: P06737 GTEx: ENSG00000100504
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P06737
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
A46 Query on A46 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth B] MOL2 format, chain F [auth A] MOL2 format, chain J [auth B] mmCIF format, chain F [auth A] mmCIF format, chain J [auth B]	F [auth A], J [auth B]	5-chloro-N-{4-[(1R)-1,2-dihydroxyethyl]phenyl}-1H-indole-2-carboxamide C₁₇ H₁₅ Cl N₂ O₃ SHCHFGSUYJUEBR-INIZCTEOSA-N		Interactions Focus chain F [auth A] Focus chain J [auth B]
PLP Query on PLP Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain I [auth B] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B] mmCIF format, chain E [auth A] mmCIF format, chain I [auth B]	E [auth A], I [auth B]	PYRIDOXAL-5'-PHOSPHATE C₈ H₁₀ N O₆ P NGVDGCNFYWLIFO-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain I [auth B]
MES Query on MES Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain H [auth B] MOL2 format, chain D [auth A] MOL2 format, chain H [auth B] mmCIF format, chain D [auth A] mmCIF format, chain H [auth B]	D [auth A], H [auth B]	2-(N-MORPHOLINO)-ETHANESULFONIC ACID C₆ H₁₃ N O₄ S SXGZJKUKBWWHRA-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain H [auth B]
GLC Query on GLC Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain G [auth B] MOL2 format, chain C [auth A] MOL2 format, chain G [auth B] mmCIF format, chain C [auth A] mmCIF format, chain G [auth B]	C [auth A], G [auth B]	alpha-D-glucopyranose C₆ H₁₂ O₆ WQZGKKKJIJFFOK-DVKNGEFBSA-N		Interactions Focus chain C [auth A] Focus chain G [auth B]
MPD Query on MPD Download Ideal Coordinates CCD File SDF format, chain K [auth B] SDF format, chain L [auth B] MOL2 format, chain K [auth B] MOL2 format, chain L [auth B] mmCIF format, chain K [auth B] mmCIF format, chain L [auth B]	K [auth B], L [auth B]	(4S)-2-METHYL-2,4-PENTANEDIOL C₆ H₁₄ O₂ SVTBMSDMJJWYQN-YFKPBYRVSA-N		Interactions Focus chain K [auth B] Focus chain L [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
A46	BindingDB: 2ZB2	IC50: 900 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.45 Å
R-Value Free: 0.307
R-Value Work: 0.261
R-Value Observed: 0.300
Space Group: P 3₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 123.819	α = 90
b = 123.819	β = 90
c = 123.538	γ = 120

Software Package:

Software Name	Purpose
CrystalClear	data collection
CNX	refinement
CrystalClear	data reduction
CrystalClear	data scaling
CNX	phasing

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2008-09-02

Deposition Author(s):

Katayama, N.

Onda, K.

Revision History (Full details and data files)

Version 1.0: 2008-09-02
Type: Initial release
Version 1.1: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.2: 2017-10-11
Changes: Refinement description
Version 1.3: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Advisory, Data collection, Database references, Derived calculations, Structure summary
Version 1.4: 2023-11-01
Changes: Data collection, Database references, Refinement description, Structure summary