4JR6

Crystal structure of DsbA from Mycobacterium tuberculosis (reduced)

4JR6 の概要

• エントリーDOI: 10.2210/pdb4jr6/pdb
• 関連するPDBエントリー: 4JR4
• 分子名称: Possible conserved membrane or secreted protein, SULFATE ION (3 entities in total)
• 機能のキーワード: thiol:disulfide oxidoreductase, thioredoxin fold, oxidoreductase, disulfide bond formation, membrane-anchored
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47553.89

構造登録者

Wang, L. (登録日: 2013-03-21, 公開日: 2013-07-17, 最終更新日: 2024-11-20)

主引用文献

Wang, L.,Li, J.,Wang, X.,Liu, W.,Zhang, X.C.,Li, X.,Rao, Z.
Structure analysis of the extracellular domain reveals disulfide bond forming-protein properties of Mycobacterium tuberculosis Rv2969c.
Protein Cell, 4:628-640, 2013

PubMed Abstract: Disulfide bond-forming (Dsb) protein is a bacterial periplasmic protein that is essential for the correct folding and disulfide bond formation of secreted or cell wallassociated proteins. DsbA introduces disulfide bonds into folding proteins, and is re-oxidized through interaction with its redox partner DsbB. Mycobacterium tuberculosis, a Gram-positive bacterium, expresses a DsbA-like protein ( Rv2969c), an extracellular protein that has its Nterminus anchored in the cell membrane. Since Rv2969c is an essential gene, crucial for disulfide bond formation, research of DsbA may provide a target of a new class of anti-bacterial drugs for treatment of M.tuberculosis infection. In the present work, the crystal structures of the extracellular region of Rv2969c (Mtb DsbA) were determined in both its reduced and oxidized states. The overall structure of Mtb DsbA can be divided into two domains: a classical thioredoxin-like domain with a typical CXXC active site, and an α-helical domain. It largely resembles its Escherichia coli homologue EcDsbA, however, it possesses a truncated binding groove; in addition, its active site is surrounded by an acidic, rather than hydrophobic surface. In our oxidoreductase activity assay, Mtb DsbA exhibited a different substrate specificity when compared to EcDsbA. Moreover, structural analysis revealed a second disulfide bond in Mtb DsbA, which is rare in the previously reported DsbA structures, and is assumed to contribute to the overall stability of Mtb DsbA. To investigate the disulphide formation pathway in M.tuberculosis, we modeled Mtb Vitamin K epoxide reductase (Mtb VKOR), a binding partner of Mtb DsbA, to Mtb DsbA.

PubMed: 23828196
DOI: 10.1007/s13238-013-3033-x

実験手法

X-RAY DIFFRACTION (1.902 Å)