3TO3

Crystal Structure of Petrobactin Biosynthesis Protein AsbB from Bacillus anthracis str. Sterne

3TO3 の概要

• エントリーDOI: 10.2210/pdb3to3/pdb
• 分子名称: Petrobactin biosynthesis protein AsbB, CHLORIDE ION, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: structural genomics, psi-biology, midwest center for structural genomics, mcsg, alpha-beta structure, adenylation, cytosol, biosynthetic protein
• 由来する生物種: Bacillus anthracis (anthrax,anthrax bacterium)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 147788.00

構造登録者

Kim, Y.,Eschenfeldt, W.,Stols, L.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG) (登録日: 2011-09-03, 公開日: 2011-10-05, 最終更新日: 2024-11-06)

主引用文献

Nusca, T.D.,Kim, Y.,Maltseva, N.,Lee, J.Y.,Eschenfeldt, W.,Stols, L.,Schofield, M.M.,Scaglione, J.B.,Dixon, S.D.,Oves-Costales, D.,Challis, G.L.,Hanna, P.C.,Pfleger, B.F.,Joachimiak, A.,Sherman, D.H.
Functional and Structural Analysis of the Siderophore Synthetase AsbB through Reconstitution of the Petrobactin Biosynthetic Pathway from Bacillus anthracis.
J.Biol.Chem., 287:16058-16072, 2012

PubMed Abstract: Petrobactin, a mixed catechol-carboxylate siderophore, is required for full virulence of Bacillus anthracis, the causative agent of anthrax. The asbABCDEF operon encodes the biosynthetic machinery for this secondary metabolite. Here, we show that the function of five gene products encoded by the asb operon is necessary and sufficient for conversion of endogenous precursors to petrobactin using an in vitro system. In this pathway, the siderophore synthetase AsbB catalyzes formation of amide bonds crucial for petrobactin assembly through use of biosynthetic intermediates, as opposed to primary metabolites, as carboxylate donors. In solving the crystal structure of the B. anthracis siderophore biosynthesis protein B (AsbB), we disclose a three-dimensional model of a nonribosomal peptide synthetase-independent siderophore (NIS) synthetase. Structural characteristics provide new insight into how this bifunctional condensing enzyme can bind and adenylate multiple citrate-containing substrates followed by incorporation of both natural and unnatural polyamine nucleophiles. This activity enables formation of multiple end-stage products leading to final assembly of petrobactin. Subsequent enzymatic assays with the nonribosomal peptide synthetase-like AsbC, AsbD, and AsbE polypeptides show that the alternative products of AsbB are further converted to petrobactin, verifying previously proposed convergent routes to formation of this siderophore. These studies identify potential therapeutic targets to halt deadly infections caused by B. anthracis and other pathogenic bacteria and suggest new avenues for the chemoenzymatic synthesis of novel compounds.

PubMed: 22408253
DOI: 10.1074/jbc.M112.359349

実験手法

X-RAY DIFFRACTION (2.382 Å)