2KID

Solution Structure of the S. Aureus Sortase A-substrate Complex

2KID の概要

• エントリーDOI: 10.2210/pdb2kid/pdb
• 関連するPDBエントリー: 1ija 1t2p
• NMR情報: BMRB: 16270
• 関連するBIRD辞書のPRD_ID: PRD_000693
• 分子名称: Sortase, (PHQ)LPA(B27) peptide, CALCIUM ION (3 entities in total)
• 機能のキーワード: sortase, eight stranded beta barrel, transpeptidase, enzyme-substrate complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Staphylococcus aureus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 17348.21

構造登録者

Suree, N.,Liew, C.K.,Villareal, V.A.,Thieu, W.,Fadeev, E.A.,Clemens, J.J.,Jung, M.E.,Clubb, R.T. (登録日: 2009-05-01, 公開日: 2009-07-21, 最終更新日: 2023-11-15)

主引用文献

Suree, N.,Liew, C.K.,Villareal, V.A.,Thieu, W.,Fadeev, E.A.,Clemens, J.J.,Jung, M.E.,Clubb, R.T.
The structure of the Staphylococcus aureus sortase-substrate complex reveals how the universally conserved LPXTG sorting signal is recognized.
J.Biol.Chem., 284:24465-24477, 2009

PubMed Abstract: In Gram-positive bacteria, sortase enzymes assemble surface proteins and pili in the cell wall envelope. Sortases catalyze a transpeptidation reaction that joins a highly conserved LPXTG sorting signal within their polypeptide substrate to the cell wall or to other pilin subunits. The molecular basis of transpeptidation and sorting signal recognition are not well understood, because the intermediates of catalysis are short lived. We have overcome this problem by synthesizing an analog of the LPXTG signal whose stable covalent complex with the enzyme mimics a key thioacyl catalytic intermediate. Here we report the solution structure and dynamics of its covalent complex with the Staphylococcus aureus SrtA sortase. In marked contrast to a previously reported crystal structure, we show that SrtA adaptively recognizes the LPXTG sorting signal by closing and immobilizing an active site loop. We have also used chemical shift mapping experiments to localize the binding site for the triglycine portion of lipid II, the second substrate to which surface proteins are attached. We propose a unified model of the transpeptidation reaction that explains the functions of key active site residues. Since the sortase-catalyzed anchoring reaction is required for the virulence of a number of bacterial pathogens, the results presented here may facilitate the development of new anti-infective agents.

PubMed: 19592495
DOI: 10.1074/jbc.M109.022624

実験手法

SOLUTION NMR