2. 1T49 Allosteric Inhibition of Protein Tyrosine Phosphatase 1B
Reference:

3. Methods
Structure-based Virtual Screening - UNITY for 1st screening of database from ‘Zinc’, Lead-Quest (4,850). - FlexS for flexible superposition of ligands. - FlexX for flexible docking.(139) - These modules are included in the SYBYL version 8.1 software (Tripos Inc.)

4. Structure-Based Virtual Screening
1st filtering by Unity 3D Search
:queries based on the PTP1B structure
(PDB id= 1T49)
2nd filtering:
Flexible superposition by FlexS
Template ; Lobaric acid
3rd filtering:
Flexible docking and scoring
by FlexX / CScore
Query used to Unity 3D search for PTP1B-selective inhibitor. Magenta ligand is the reported PTP1B inhibitor

5. A Drug-enzyme Binding Model
Changon Seo et al., 2009

6. Noncompetitive Inhibitors of PTP1B
Christian Wiesmann et al., 2004

7. Docking Modes of Active Compounds into Allosteric Site
Compound 1 (Lobaric acid)
Compound 1 (Carboxylate form)
Compound 2
Compound 3
Compound 8
Compound 9

8. Active Ligands by Flexible Superposition
Benzene ring interacting with Phe280
H-bonding with Asn193
Two hydrophobic alkyl chains

9. An Active Ligand inhibiting PTP1B activity
Zinc
(Score: )
Lobaric acid (Score: )
Hydrophobicity Potential (PDB id: 1T49)

10. References
Changon Seo, Jae Hak Sohn, Jong Seog Ahn, Joung Han Yim, Hong Kum Lee, Hyuncheol Oh (2009) Protein tyrosine phosphatase 1B inhibitory effects of depsidone and pseudodepsidone metabolites from the Antarctic lichen Stereocaulon alpinum, Bioorganic & Medicinal Chemistry Letters –2803
Christian Wiesmann, Kenneth J Barr, Jenny Kung, Jiang Zhu, Daniel A Erlanson, Wang Shen, Bruce J Fahr, Min Zhong, Lisa Taylor, Mike Randal, Robert S McDowell & Stig K Hansen (2004) Allosteric inhibition of protein tyrosine phosphatase 1B, Nature Structural & Molecular Biology  11,