3UFA

Crystal structure of the staphylococcal serine protease SplA in complex with a specific phosphonate inhibitor

3UFA の概要

• エントリーDOI: 10.2210/pdb3ufa/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000908
• 分子名称: Serine protease splA, N-(3-carboxypropanoyl)-L-valyl-N-[(1S)-2-phenyl-1-phosphonoethyl]-L-prolinamide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: chymotrypsin like fold, serine protease, extracellular protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Staphylococcus aureus
• 細胞内の位置: Secreted: Q2FXC2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44872.28

構造登録者

Zdzalik, M.,Pietrusewicz, E.,Pustelny, K.,Stec-Niemczyk, J.,Popowicz, G.M.,Potempa, J.,Oleksyszyn, J.,Dubin, G. (登録日: 2011-10-31, 公開日: 2013-01-23, 最終更新日: 2024-10-30)

主引用文献

Burchacka, E.,Zdzalik, M.,Niemczyk, J.S.,Pustelny, K.,Popowicz, G.,Wladyka, B.,Dubin, A.,Potempa, J.,Sienczyk, M.,Dubin, G.,Oleksyszyn, J.
Development and binding characteristics of phosphonate inhibitors of SplA protease from Staphylococcus aureus.
Protein Sci., 23:179-189, 2014

PubMed Abstract: Staphylococcus aureus is responsible for a variety of human infections, including life-threatening, systemic conditions. Secreted proteome, including a range of proteases, constitutes the major virulence factor of the bacterium. However, the functions of individual enzymes, in particular SplA protease, remain poorly characterized. Here, we report development of specific inhibitors of SplA protease. The design, synthesis, and activity of a series of α-aminoalkylphosphonate diaryl esters and their peptidyl derivatives are described. Potent inhibitors of SplA are reported, which may facilitate future investigation of physiological function of the protease. The binding modes of the high-affinity compounds Cbz-Phe(P) -(OC6 H4 -4-SO2 CH3 )2 and Suc-Val-Pro-Phe(P) -(OC6 H5 )2 are revealed by high-resolution crystal structures of complexes with the protease. Surprisingly, the binding mode of both compounds deviates from previously characterized canonical interaction of α-aminoalkylphosphonate peptidyl derivatives and family S1 serine proteases.

PubMed: 24375505
DOI: 10.1002/pro.2403

実験手法

X-RAY DIFFRACTION (1.8 Å)