3O82

Structure of BasE N-terminal domain from Acinetobacter baumannii bound to 5'-O-[N-(2,3-dihydroxybenzoyl)sulfamoyl] adenosine

3O82 の概要

• エントリーDOI: 10.2210/pdb3o82/pdb
• 関連するPDBエントリー: 3O83 3O84
• 分子名称: Peptide arylation enzyme, 5'-O-{[(2,3-dihydroxyphenyl)carbonyl]sulfamoyl}adenosine, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: ligase, adenylation of 2, 3-dihydroxybenzoate and transfer to pantetheine cofactor of basf, non-ribosomal peptide synthetase (nrps)
• 由来する生物種: Acinetobacter baumannii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 122861.70

構造登録者

Drake, E.J.,Duckworth, B.P.,Neres, J.,Aldrich, C.C.,Gulick, A.M. (登録日: 2010-08-02, 公開日: 2010-10-06, 最終更新日: 2023-09-06)

主引用文献

Drake, E.J.,Duckworth, B.P.,Neres, J.,Aldrich, C.C.,Gulick, A.M.
Biochemical and structural characterization of bisubstrate inhibitors of BasE, the self-standing nonribosomal peptide synthetase adenylate-forming enzyme of acinetobactin synthesis.
Biochemistry, 49:9292-9305, 2010

PubMed Abstract: The human pathogen Acinetobacter baumannii produces a siderophore called acinetobactin that is derived from one molecule each of threonine, histidine, and 2,3-dihydroxybenzoic acid (DHB). The activity of several nonribosomal peptide synthetase (NRPS) enzymes is used to combine the building blocks into the final molecule. The acinetobactin synthesis pathway initiates with a self-standing adenylation enzyme, BasE, that activates the DHB molecule and covalently transfers it to the pantetheine cofactor of an aryl-carrier protein of BasF, a strategy that is shared with many siderophore-producing NRPS clusters. In this reaction, DHB reacts with ATP to form the aryl adenylate and pyrophosphate. In a second partial reaction, the DHB is transferred to the carrier protein. Inhibitors of BasE and related enzymes have been identified that prevent growth of bacteria on iron-limiting media. Recently, a new inhibitor of BasE has been identified via high-throughput screening using a fluorescence polarization displacement assay. We present here biochemical and structural studies to examine the binding mode of this inhibitor. The kinetics of the wild-type BasE enzyme is shown, and inhibition studies demonstrate that the new compound exhibits competitive inhibition against both ATP and 2,3-dihydroxybenzoate. Structural examination of BasE bound to this inhibitor illustrates a novel binding mode in which the phenyl moiety partially fills the enzyme pantetheine binding tunnel. Structures of rationally designed bisubstrate inhibitors are also presented.

PubMed: 20853905
DOI: 10.1021/bi101226n

実験手法

X-RAY DIFFRACTION (2.7 Å)