3ZCB

VbhT Fic protein from Bartonella schoenbuchensis in complex with VbhA antitoxin mutant E24G and ATP

3ZCB の概要

• エントリーDOI: 10.2210/pdb3zcb/pdb
• 関連するPDBエントリー: 3ZC7 3ZCN
• 分子名称: ADENOSINE MONOPHOSPHATE-PROTEIN TRANSFERASE VBHT, ANTITOXIN VBHA, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: transferase-antitoxin complex, ampylation, adenylylation, toxin-antitoxin complex, transferase/antitoxin
• 由来する生物種: BARTONELLA SCHOENBUCHENSIS; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31007.69

構造登録者

Goepfert, A.,Schirmer, T. (登録日: 2012-11-19, 公開日: 2013-06-19, 最終更新日: 2023-12-20)

主引用文献

Goepfert, A.,Stanger, F.V.,Dehio, C.,Schirmer, T.
Conserved Inhibitory Mechanism and Competent ATP Binding Mode for Adenylyltransferases with Fic Fold.
Plos One, 8:64901-, 2013

PubMed Abstract: The ubiquitous FIC domain is evolutionarily conserved from bacteria to human and has been shown to catalyze AMP transfer onto protein side-chain hydroxyl groups. Recently, it was predicted that most catalytically competent Fic proteins are inhibited by the presence of an inhibitory helix αinh that is provided by a cognate anti-toxin (class I), or is part of the N- or C-terminal part of the Fic protein itself (classes II and III). In vitro, inhibition is relieved by mutation of a conserved glutamate of αinh to glycine. For the class III bacterial Fic protein NmFic from Neisseria meningitidis, the inhibitory mechanism has been elucidated. Here, we extend above study by including bacterial class I and II Fic proteins VbhT from Bartonella schoenbuchensis and SoFic from Shewanella oneidensis, respectively, and the respective E->G mutants. Comparative enzymatic and crystallographic analyses show that, in all three classes, the ATP substrate binds to the wild-type FIC domains, but with the α-phosphate in disparate and non-competent orientations. In the E->G mutants, however, the tri-phosphate moiety is found reorganized to the same tightly bound structure through a unique set of hydrogen bonds with Fic signature motif residues. The γ-phosphate adopts the location that is taken by the inhibitory glutamate in wild-type resulting in an α-phosphate orientation that can be attacked in-line by a target side-chain hydroxyl group. The latter is properly registered to the Fic active center by main-chain β-interactions with the β-hairpin flap. These data indicate that the active site motif and the exposed edge of the flap are both required to form an adenylylation-competent Fic protein.

PubMed: 23738009
DOI: 10.1371/JOURNAL.PONE.0064901

実験手法

X-RAY DIFFRACTION (1.94 Å)