6M9U

Structure of the apo-form of 20beta-Hydroxysteroid Dehydrogenase from Bifidobacterium adolescentis strain L2-32

6M9U の概要

• エントリーDOI: 10.2210/pdb6m9u/pdb
• 分子名称: Oxidoreductase, short chain dehydrogenase/reductase family protein, ISOPROPYL ALCOHOL, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (10 entities in total)
• 機能のキーワード: pyridine nucleotide-dependent enzyme, short-chain dehydrogenase/reductase, nadh dependent, oxidoreductase
• 由来する生物種: Bifidobacterium adolescentis L2-32
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63797.74

構造登録者

Mythen, S.M.,Pollet, R.M.,Koropatkin, N.M.,Ridlon, J.M. (登録日: 2018-08-24, 公開日: 2019-06-26, 最終更新日: 2023-10-11)

主引用文献

Doden, H.L.,Pollet, R.M.,Mythen, S.M.,Wawrzak, Z.,Devendran, S.,Cann, I.,Koropatkin, N.M.,Ridlon, J.M.
Structural and biochemical characterization of 20 beta-hydroxysteroid dehydrogenase fromBifidobacterium adolescentisstrain L2-32.
J.Biol.Chem., 294:12040-12053, 2019

PubMed Abstract: Anaerobic bacteria inhabiting the human gastrointestinal tract have evolved various enzymes that modify host-derived steroids. The bacterial steroid-17,20-desmolase pathway cleaves the cortisol side chain, forming pro-androgens predicted to impact host physiology. Bacterial 20β-hydroxysteroid dehydrogenase (20β-HSDH) regulates cortisol side-chain cleavage by reducing the C-20 carboxyl group on cortisol, yielding 20β-dihydrocortisol. Recently, the gene encoding 20β-HSDH in ATCC 43058 was reported, and a nonredundant protein search yielded a candidate β- gene in strain L2-32. 20β-HSDH could regulate cortisol side-chain cleavage by limiting pro-androgen formation in bacteria such as and 21-dehydroxylation by Here, the putative 20β-HSDH was cloned, overexpressed, and purified. 20β-HSDH activity was confirmed through whole-cell and pure enzymatic assays, and it is specific for cortisol. Next, we solved the structures of recombinant 20β-HSDH in both the apo- and holo-forms at 2.0-2.2 Å resolutions, revealing close overlap except for rearrangements near the active site. Interestingly, the structures contain a large, flexible N-terminal region that was investigated by gel-filtration chromatography and CD spectroscopy. This extended N terminus is important for protein stability because deletions of varying lengths caused structural changes and reduced enzymatic activity. A nonconserved extended N terminus was also observed in several short-chain dehydrogenase/reductase family members. strains capable of 20β-HSDH activity could alter glucocorticoid metabolism in the gut and thereby serve as potential probiotics for the management of androgen-dependent diseases.

PubMed: 31209107
DOI: 10.1074/jbc.RA119.009390

実験手法

X-RAY DIFFRACTION (2.2 Å)