9R7A

Imine Reductase IR91 from Kribbella flavida with NADP+ and 5-methoxy-(S)-2-(N-methylamino)tetralin

This is a non-PDB format compatible entry.

Summary for 9R7A

• Entry DOI: 10.2210/pdb9r7a/pdb
• Descriptor: 6-phosphogluconate dehydrogenase NAD-binding protein, SULFATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• Functional Keywords: amine, imine, nadph, imine reductase, oxidoreductase
• Biological source: Kribbella flavida
• Total number of polymer chains: 2
• Total formula weight: 63823.33

Authors

Srinivas, K.,Gilio, A.K.,Grogan, G. (deposition date: 2025-05-14, release date: 2025-11-05)

Primary citation

Srinivas, K.,Gilio, A.K.,Sharma, M.,Green, L.,Ascham, A.,Domenech, J.,Pogranyi, B.,Li, J.,France, S.P.,Lewis, R.D.,Unsworth, W.P.,Grogan, G.
Structures of "Tyrosine-IRED" IR91 from Kribbella flavida in Complex with a Reductive Amination Substrate and Product.
Chembiochem, 26:e202500450-e202500450, 2025

PubMed Abstract: Imine reductases with an (S)-preference for the reduction of the model substrate 2-methyl pyrroline typically contain tyrosine in the active site (Y-IREDs) instead of the aspartate present within (R)-selective enzymes (D-IREDs). As with D-IREDs, a subset of Y-IREDs is capable of enabling reductive amination reactions between some ketone and amine partners to give optically active amines with high optical purity. However, structures of Y-IREDs in complex with the substrates and products of the reductive amination have not been forthcoming. Herein, structures of the Y-IRED IR91 from Kribbella flavida in complex with 5-methoxy-2-tetralone, a synthetic precursor to the anti-Parkinson's treatment rotigotine, and also its reductive amination product with methylamine, 5-methoxy-(S)-2-(N-methylamino)-tetralin, are presented. The structures, in combination with mutation and kinetic studies, support a role for tryptophan residue W258 in the activity of the enzyme, possibly in binding of the ketone prior to reaction with methylamine.

PubMed: 40727968
DOI: 10.1002/cbic.202500450

Experimental method

X-RAY DIFFRACTION (1.91 Å)