Exosites: beyond the limitations of the protease active site

被引:0
作者
Izaguirre, Gonzalo [1 ,2 ]
机构
[1] Insight DNA, Oak Pk, IL 60302 USA
[2] Univ Illinois, Coll Dent, Chicago, IL USA
关键词
cofactors; exosites; heparin; proteases; serpins;
D O I
10.1111/febs.70057
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Proteases rely on their active sites for substrate specificity, but these sites have inherent limitations that impact enzymatic efficiency and regulation. Exosites and cofactors help overcome these constraints by enhancing the protease's substrate interactions, specificity, and inhibition. Recent research by Gangemi et al. highlights the role of exosites in regulating the inhibition of the protease neutrophil elastase by the serpin alpha-1-antitrypsin. Understanding these mechanisms is crucial for developing therapeutic applications. Advances in computational analysis provide new insights into exosite function, complementing traditional structural studies and expanding potential biotechnological applications of protease inhibitors.
引用
收藏
页数:3
相关论文
共 4 条
[1]   Identification of an exosite at the neutrophil elastase/alpha-1-antitrypsin interface [J].
Gangemi, Roberto ;
Bignotti, Mattia ;
Denardo, Andrea ;
Pearce, Claudia N. ;
Ronzoni, Riccardo ;
Lomas, David A. ;
Irving, James A. ;
Fra, Annamaria ;
Gangemi, Fabrizio .
FEBS JOURNAL, 2025, :1887-1903
[2]   Thrombin inhibition by the serpins [J].
Huntington, J. A. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2013, 11 :254-264
[3]   Conformational Activation of Antithrombin by Heparin Involves an Altered Exosite Interaction with Protease [J].
Izaguirre, Gonzalo ;
Aguila, Sonia ;
Qi, Lixin ;
Swanson, Richard ;
Roth, Ryan ;
Rezaie, Alireza R. ;
Gettins, Peter G. W. ;
Olson, Steven T. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (49) :34049-34064
[4]   Engineering the serpin α1-antitrypsin: A diversity of goals and techniques [J].
Scott, Benjamin M. ;
Sheffield, William P. .
PROTEIN SCIENCE, 2020, 29 (04) :856-871