6ISV

Structure of acetophenone reductase from Geotrichum candidum NBRC 4597 in complex with NAD

Summary for 6ISV

• Entry DOI: 10.2210/pdb6isv/pdb
• Descriptor: Acetophenone reductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ZINC ION, ... (4 entities in total)
• Functional Keywords: nad binding, oxidoreductase
• Biological source: Geotrichum candidum (Oospora lactis)
• Total number of polymer chains: 2
• Total formula weight: 82268.10

Authors

Koesoema, A.A.,Sugiyama, Y.,Senda, M.,Senda, T.,Matsuda, T. (deposition date: 2018-11-19, release date: 2019-09-11, Last modification date: 2024-03-27)

Primary citation

Koesoema, A.A.,Sugiyama, Y.,Xu, Z.,Standley, D.M.,Senda, M.,Senda, T.,Matsuda, T.
Structural basis for a highly (S)-enantioselective reductase towards aliphatic ketones with only one carbon difference between side chain.
Appl.Microbiol.Biotechnol., 103:9543-9553, 2019

PubMed Abstract: Aliphatic ketones, such as 2-butanone and 3-hexanone, with only one carbon difference among side chains adjacent to the carbonyl carbon are difficult to be reduced enantioselectively. In this study, we utilized an acetophenone reductase from Geotrichum candidum NBRC 4597 (GcAPRD) to reduce challenging aliphatic ketones such as 2-butanone (methyl ethyl ketone) and 3-hexanone (ethyl propyl ketone) to their corresponding (S)-alcohols with 94% ee and > 99% ee, respectively. Through crystallographic structure determination, it was suggested that residue Trp288 limit the size of the small binding pocket. Docking simulations imply that Trp288 plays an important role to form a C-H⋯π interaction for proper orientation of ketones in the pro-S binding pose in order to produce (S)-alcohols. The excellent (S)-enantioselectivity is due to a non-productive pro-R binding pose, consistent with the observation that the (R)-alcohol acts as an inhibitor of (S)-alcohol oxidation.

PubMed: 31482280
DOI: 10.1007/s00253-019-10093-w

Experimental method

X-RAY DIFFRACTION (2.5 Å)