title: Substrate specificity of human matriptase-2.
abstract: Human matriptase-2 is an enzyme that belongs to the family of type II transmembrane serine proteases. So far there is a limited knowledge regarding its specificity and protein substrate(s). One of the identified natural substrates is hemojuvelin, a protein involved in the control of iron homeostasis. In this work, we describe the synthesis and evaluation of internal quenched substrates using a combinatorial approach. The iterative deconvolution of two libraries to define the specificity of matriptase-2 yielded to the identification of the substrate ABZ-Ile-Arg-Ala-Arg-Ser-Ala-Gly-Tyr(3-NO2)-NH2 with a k(cat)/K(m) value of 4.5 × 10(5) M(-1) × s(-1), i.e. the highest specificity constant reported so far for matriptase-2.
authors.affiliation: Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Wysocka
authors.affiliation: Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland.
authors.forename: N
authors.initials: N
authors.lastname: Gruba
authors.affiliation: Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Miecznikowska
authors.affiliation: Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Popow-Stellmaszyk
authors.affiliation: Pharmaceutical Institute, Rheinische Friedrich-Wilhelms-Universität, An der Immenburg 4, 53121 Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gütschow
authors.affiliation: Pharmaceutical Institute, Rheinische Friedrich-Wilhelms-Universität, An der Immenburg 4, 53121 Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stirnberg
authors.affiliation: Pharmaceutical Institute, Rheinische Friedrich-Wilhelms-Universität, An der Immenburg 4, 53121 Bonn, Germany; Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, 53113 Bonn, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Furtmann
authors.affiliation: Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, 53113 Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
authors.affiliation: Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland. Electronic address: alesner@chem.univ.gda.pl.
authors.forename: A
authors.initials: A
authors.lastname: Lesner
authors.affiliation: Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-952 Gdansk, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Rolka
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D019151:Peptide Library; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D008565:Membrane Proteins; D009842:Oligopeptides; D019151:Peptide Library; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; C467801:matriptase 2
keywords: Combinatorial chemistry; Fluorogenic substrates; Internally quenched substrates; Matriptase-2