Hydrolytic protein cleavage mediated by unusual mononuclear copper(II) complexes: X-ray structures and solution studies.
The crystal structures and redox and UV-vis/EPR spectroscopic properties of two new mononuclear copper(II) complexes, [Cu(HL1)Cl2] (1) and [Cu(L1)Cl] (2), prepared through the reaction between copper(II) chloride and the ligand 2-[(bis(pyridylmethyl)amino)methyl]-4-methyl-6-formylphenol (HL1) under distinct base conditions, are reported along with solution studies. Also, we demonstrate that these CuII complexes are able to cleave unactivated peptide bonds from bovine serum albumin (BSA) and the thermostable enzyme Taq DNA polymerase at micromolar concentration, under mild pH and temperature conditions. The cleavage activity seems to be specific with defined proteolytic fragments appearing after protein treatment. The location of the specific cleavage sites was tentatively assigned to solvent-accessible portions of the protein. These are two of the most active Cu(II) complexes described to date, since their cleavage activity is detected in minutes and evidence is here presented for a hydrolytic mechanism mediating protein cleavage by these complexes.
de Oliveira
Mauricio C B
MC
Laboratório de Expressão Gênica, Departamento de Bioquímica-CCB, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
Scarpellini
Marciela
M
Neves
Ademir
A
Terenzi
Hernán
H
Bortoluzzi
Adailton J
AJ
Szpoganics
Bruno
B
Greatti
Alessandra
A
Mangrich
Antônio S
AS
de Souza
Emanuel M
EM
Fernandez
Pablo M
PM
Soares
Marcia R
MR
D000818:Animals; D002413:Cations, Divalent; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004563:Electrochemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D019914:Taq Polymerase / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
D002413:Cations, Divalent; D008024:Ligands; D009942:Organometallic Compounds; D010446:Peptide Fragments; D011506:Proteins; D012709:Serum Albumin; D012996:Solutions; D003300:Copper; D004247:DNA; D019914:Taq Polymerase