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Insights into Matriptase‐2 Substrate Binding and Inhibition Mechanisms by Analyzing Active‐Site‐Mutated Variants
Author(s) -
Maurer Eva,
Sisay Mihiret T.,
Stirnberg Marit,
Steinmetzer Torsten,
Bajorath Jürgen,
Gütschow Michael
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100350
Subject(s) - serine protease , active site , chemistry , mutagenesis , regulator , binding site , enzyme , substrate (aquarium) , biochemistry , serine , site directed mutagenesis , protease , mutation , biology , mutant , gene , ecology
Matriptase‐2 is a type II transmembrane serine protease that functions as key regulator of body iron homeostasis. To obtain insights into substrate/inhibitor–enzyme interactions, site‐directed mutagenesis, kinetic and molecular modeling studies were performed. Based on the active site structure of the related enzyme matriptase, amino acids that enhanced (Phe 665) or reduced (Asp 785, Tyr 712) the affinity of peptide ligands for matriptase‐2 were identified.