6I6C

SEPIAPTERIN REDUCTASE IN COMPLEX WITH COMPOUND 2

6I6C の概要

• エントリーDOI: 10.2210/pdb6i6c/pdb
• 分子名称: Sepiapterin reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (1~{R},2~{S},4~{S})-~{N}-(3-chloranyl-4-cyano-phenyl)sulfonylbicyclo[2.2.1]heptane-2-carboxamide, ... (5 entities in total)
• 機能のキーワード: sepiapterin-reductase, oxidoreductase, proteros biostructures gmbh
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62495.83

構造登録者

Alen, J.,Schade, M.,Wagener, M.,Blaesse, M. (登録日: 2018-11-15, 公開日: 2019-07-10, 最終更新日: 2024-05-15)

主引用文献

Alen, J.,Schade, M.,Wagener, M.,Christian, F.,Nordhoff, S.,Merla, B.,Dunkern, T.R.,Bahrenberg, G.,Ratcliffe, P.
Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors.
J.Med.Chem., 62:6391-6397, 2019

PubMed 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 F 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.

PubMed: 31244106
DOI: 10.1021/acs.jmedchem.9b00218

実験手法

X-RAY DIFFRACTION (1.72 Å)