2H04

Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with inhibitors

PDB DOI: https://doi.org/10.2210/pdb2H04/pdb

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

Deposited: 2006-05-13 Released: 2006-06-13
Deposition Author(s): Evdokimov, A.G., Pokross, M.E., Walter, R.L., Mekel, M., Gray, J.L., Peters, K.G., Maier, M.B., Amarasinghe, K.D., Clark, C.M., Nichols, R.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.30 Å
R-Value Free: 0.238
R-Value Work: 0.169
R-Value Observed: 0.170

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta.

Amarasinghe, K.K., Evdokimov, A.G., Xu, K., Clark, C.M., Maier, M.B., Srivastava, A., Colson, A.O., Gerwe, G.S., Stake, G.E., Howard, B.W., Pokross, M.E., Gray, J.L., Peters, K.G.

(2006) Bioorg Med Chem Lett 16: 4252-4256

PubMed: 16759857 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2006.05.074
Primary Citation of Related Structures:
2H02, 2H03, 2H04

PubMed Abstract:
The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPbeta. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPbeta potency.

Organizational Affiliation

Procter & Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA. Amarasinghe.kk@pg.com

Macromolecule Content

Total Structure Weight: 36.74 kDa
Atom Count: 2,473
Modelled Residue Count: 280
Deposited Residue Count: 313
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Protein tyrosine phosphatase, receptor type, B,	A	313	Homo sapiens	Mutation(s): 0 Gene Names: PTPRB EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for P23467 (Homo sapiens) Explore P23467 Go to UniProtKB: P23467
PHAROS: P23467 GTEx: ENSG00000127329
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P23467
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
4UN Query on 4UN Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	{4-[2,2-BIS(5-METHYL-1,2,4-OXADIAZOL-3-YL)-3-PHENYLPROPYL]PHENYL}SULFAMIC ACID C₂₁ H₂₁ N₅ O₅ S SXDBFKLPNPUPRI-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
4UN	Binding MOAD: 2H04	IC50: 70 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.30 Å
R-Value Free: 0.238
R-Value Work: 0.169
R-Value Observed: 0.170
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 44.803	α = 90
b = 70.12	β = 90
c = 90.722	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
PDB_EXTRACT	data extraction
MAR345	data collection
HKL-2000	data scaling
AMoRE	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2006-06-13

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2006-06-13
Type: Initial release
Version 1.1: 2008-05-01
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2017-10-18
Changes: Refinement description
Version 1.4: 2023-08-30
Changes: Data collection, Database references, Derived calculations, Refinement description