6Y4D

Crystal structure of a short-chain dehydrogenase/reductase (SDR) from Zephyranthes treatiae in complex with NADP+

Summary for 6Y4D

• Entry DOI: 10.2210/pdb6y4d/pdb
• Descriptor: short-chain dehydrogenase/reductase (SDR), NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: asymmetric reduction, biocatalysis, imine reduction, mutagenesis, rational design, short-chain dehydrogenase/reductase, zephyranthes treatiae, complex, oxidoreductase
• Biological source: Zephyranthes treatiae
• Total number of polymer chains: 2
• Total formula weight: 63931.54

Authors

Sautner, V.,Steimle, S.,Roth, S.,Mueller, M.,Tittmann, K. (deposition date: 2020-02-20, release date: 2020-04-29, Last modification date: 2024-01-24)

Primary citation

Roth, S.,Stockinger, P.,Steff, J.,Steimle, S.,Sautner, V.,Tittmann, K.,Pleiss, J.,Muller, M.
Crossing the Border: From Keto- to Imine Reduction in Short-Chain Dehydrogenases/Reductases.
Chembiochem, 21:2615-2619, 2020

PubMed Abstract: The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the "classical" SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes.

PubMed: 32315494
DOI: 10.1002/cbic.202000233

Experimental method

X-RAY DIFFRACTION (2.1 Å)