PDBsum entry 6i6f

Oxidoreductase

PDB id: 6i6f

Contents

Protein chains

265 a.a.

Ligands

NAP ×2

H4E

EDO ×13

Waters ×210

References listed in PDB file

Key reference

• Title: Fragment-Based discovery of novel potent sepiapterin reductase inhibitors.
• Authors: J.Alen, M.Schade, M.Wagener, F.Christian, S.Nordhoff, B.Merla, T.R.Dunkern, G.Bahrenberg, P.Ratcliffe.
• Ref.: J Med Chem, 2019, 62, 6391-6397. [DOI no: 10.1021/acs.jmedchem.9b00218]
• PubMed id: 31244106

Abstract

Genome-wide-association studies in chronic low back pain patients identified sepiapterin reductase as a high interest target for developing new analgesics. Here we used ¹⁹F NMR fragment screening for the discovery of novel, ligand-efficient SPR inhibitors. We report the crystal structures of six chemically diverse inhibitors complexed with SPR, identifying relevant interactions and binding modes in the sepiapterin pocket. Exploration of our initial fragment screening hit led to double-digit nanomolar inhibitors of SPR with excellent ligand efficiency.