MAP Kinase Phosphatase Docking Studies

Molecular Docking Studies of Pyrrole Carboxamide Library

• Brummond Library (10 active compounds) (Werner et al., J. Comb. Chem., 2006)
  These are the docking results for the compounds studied in JPET article.
  John S. Lazo, John J. Skoko, Stefan Werner, Branko Mitasev, Ahmet Bakan, Fumito Koizumi, Archibong Yellow-Duke, Ivet Bahar, and Kay M. Brummond (2007) Structurally Unique Inhibitors of Human Mitogen-Activated Protein Kinase Phosphatase-1 Identified in a Pyrrole Carboxamide Library Journal of Pharmacology And Experimental Therapeutics 323(3):940-947.

Methodology

MKP-1 (DUSP1) does not have a structure deposited in Protein Data Bank.  However, there are several structures of catalytic domains of closely related Dual-specifity Phosphatases (DUSP).  These structures are:

• VH3 (DUSP9) catalytic domain at active state (PDB id: 2G6Z), 64% sequence identity to MKP-1
• MKP-4 (DUSP9) catalytic domain at active state (PDB id: 2HXP), 49% sequence identity to MKP-1
• MKP-5 (DUSP10) catalytic domain at active state (PDB id: 1ZZW), 46% sequence identity to MKP-1
• PAC1 (DUSP2) catalytic domain at inactive state (PDB id: 1M3G), 74% sequence identity to MKP-1
• MKP-3 (DUSP6) catalytic domain at inactive state (PDB id: 1MKP), 49% sequence identity to MKP-1

Our models are based on the catalytic domain structures at active state and are generated using MODELLER 9v1. GOLD v3.1 is used for molecular docking.