PDBsum entry 1z6j

Hydrolase

PDB id: 1z6j

Contents

Protein chains

142 a.a.

254 a.a.

207 a.a.

Ligands

PY3

Metals

_MG

_CA ×2

Waters ×389

References listed in PDB file

Key reference

• Title: Structure-Based design and synthesis of pyrazinones containing novel p1 'Side pocket' Moieties as inhibitors of tf/viia.
• Authors: B.A.Schweitzer, W.L.Neumann, H.K.Rahman, C.L.Kusturin, K.R.Sample, G.I.Poda, R.G.Kurumbail, A.M.Stevens, R.A.Stegeman, W.C.Stallings, M.S.South.
• Ref.: Bioorg Med Chem Lett, 2005, 15, 3006-3011. [DOI no: 10.1016/j.bmcl.2005.04.037]
• PubMed id: 15913999

Abstract

We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.

Secondary reference #1

• Title: Structure-Based drug design of pyrazinone antithrombotics as selective inhibitors of the tissue factor viia complex.
• Authors: M.S.South, B.L.Case, R.S.Wood, D.E.Jones, M.J.Hayes, T.J.Girard, R.M.Lachance, N.S.Nicholson, M.Clare, A.M.Stevens, R.A.Stegeman, W.C.Stallings, R.G.Kurumbail, J.J.Parlow.
• Ref.: Bioorg Med Chem Lett, 2003, 13, 2319-2325. [DOI no: 10.1016/S0960-894X(03)00410-4]
• PubMed id: 12824026

Secondary reference #2

• Title: Polymer-Assisted solution-Phase library synthesis and crystal structure of alpha-Ketothiazoles as tissue factor viia inhibitors.
• Authors: J.J.Parlow, T.A.Dice, R.M.Lachance, T.J.Girard, A.M.Stevens, R.A.Stegeman, W.C.Stallings, R.G.Kurumbail, M.S.South.
• Ref.: J Med Chem, 2003, 46, 4043-4049. [DOI no: 10.1021/jm030130t]
• PubMed id: 12954057