8VCW

X-Ray Crystal Structure of the biotin synthase from B. obeum

8VCW の概要

• エントリーDOI: 10.2210/pdb8vcw/pdb
• 分子名称: Biotin synthase, S-ADENOSYLMETHIONINE, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (9 entities in total)
• 機能のキーワード: biotin, iron sulfur cluster, desthiobiotin, radical sam, transferase
• 由来する生物種: Blautia obeum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37980.99

構造登録者

Lachowicz, J.C.,Grove, T.L. (登録日: 2023-12-14, 公開日: 2024-01-24, 最終更新日: 2024-02-07)

主引用文献

Lachowicz, J.C.,Lennox-Hvenekilde, D.,Myling-Petersen, N.,Salomonsen, B.,Verkleij, G.,Acevedo-Rocha, C.G.,Caddell, B.,Gronenberg, L.S.,Almo, S.C.,Sommer, M.O.A.,Genee, H.J.,Grove, T.L.
Discovery of a Biotin Synthase That Utilizes an Auxiliary 4Fe-5S Cluster for Sulfur Insertion.
J.Am.Chem.Soc., 146:1860-1873, 2024

PubMed Abstract: Biotin synthase (BioB) is a member of the Radical SAM superfamily of enzymes that catalyzes the terminal step of biotin (vitamin B7) biosynthesis, in which it inserts a sulfur atom in desthiobiotin to form a thiolane ring. How BioB accomplishes this difficult reaction has been the subject of much controversy, mainly around the source of the sulfur atom. However, it is now widely accepted that the sulfur atom inserted to form biotin stems from the sacrifice of the auxiliary 2Fe-2S cluster of BioB. Here, we bioinformatically explore the diversity of BioBs available in sequence databases and find an unexpected variation in the coordination of the auxiliary iron-sulfur cluster. After characterization, including the determination of biotin formation and representative crystal structures, we report a new type of BioB utilized by virtually all obligate anaerobic organisms. Instead of a 2Fe-2S cluster, this novel type of BioB utilizes an auxiliary 4Fe-5S cluster. Interestingly, this auxiliary 4Fe-5S cluster contains a ligated sulfide that we propose is used for biotin formation. We have termed this novel type of BioB, Type II BioB, with the 2Fe-2S cluster sacrificial BioB representing Type I. This surprisingly ubiquitous Type II BioB has implications for our understanding of the function and evolution of Fe-S clusters in enzyme catalysis, highlighting the difference in strategies between the anaerobic and aerobic world.

PubMed: 38215281
DOI: 10.1021/jacs.3c05481

実験手法

X-RAY DIFFRACTION (1.35 Å)