8DKO

Minimal PutA proline dehydrogenase domain (design #1) complexed with S-(-)-tetrahydro-2-furoic acid

8DKO の概要

• エントリーDOI: 10.2210/pdb8dko/pdb
• 分子名称: Bifunctional protein PutA, FLAVIN-ADENINE DINUCLEOTIDE, TETRAHYDROFURAN-2-CARBOXYLIC ACID, ... (4 entities in total)
• 機能のキーワード: beta/alpha barrel, flavoenzyme, proline catabolism, oxidoreductase
• 由来する生物種: Sinorhizobium meliloti SM11; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92613.24

構造登録者

Tanner, J.J.,Bogner, A.N. (登録日: 2022-07-05, 公開日: 2022-12-14, 最終更新日: 2023-10-25)

主引用文献

Bogner, A.N.,Ji, J.,Tanner, J.J.
Structure-based engineering of minimal proline dehydrogenase domains for inhibitor discovery.
Protein Eng.Des.Sel., 35:-, 2022

PubMed Abstract: Proline dehydrogenase (PRODH) catalyzes the FAD-dependent oxidation of l-proline to Δ1-pyrroline-5-carboxylate and is a target for inhibitor discovery because of its importance in cancer cell metabolism. Because human PRODH is challenging to purify, the PRODH domains of the bacterial bifunctional enzyme proline utilization A (PutA) have been used for inhibitor development. These systems have limitations due to large polypeptide chain length, conformational flexibility and the presence of domains unrelated to PRODH activity. Herein, we report the engineering of minimal PRODH domains for inhibitor discovery. The best designs contain one-third of the 1233-residue PutA from Sinorhizobium meliloti and include a linker that replaces the PutA α-domain. The minimal PRODHs exhibit near wild-type enzymatic activity and are susceptible to known inhibitors and inactivators. Crystal structures of minimal PRODHs inhibited by S-(-)-tetrahydro-2-furoic acid and 2-(furan-2-yl)acetic acid were determined at 1.23 and 1.72 Å resolution. Minimal PRODHs should be useful in chemical probe discovery.

PubMed: 36448708
DOI: 10.1093/protein/gzac016

実験手法

X-RAY DIFFRACTION (1.8 Å)