title: Capreomycin--a polypeptide antitubercular antibiotic with unusual binding properties toward copper(II).
abstract: Capreomycin is an important therapeutic agent having intriguing and diverse molecular features. Its polypeptidic structure rich in nitrogen donors makes the drug a promising chelating agent for a number of transition metal ions, especially for copper(II). The results of the model investigational studies suggest that capreomycin anchors Cu(2+) ion with an amino function of the α,β-diaminopropionic acid residue at pH around 5. At physiological pH copper(II) ion is coordinated by two deprotonated amide nitrogen atoms of the α,β-diaminopropionic acid, the serine residue as well as the amino function deriving from the β-lysine. Above that pH value we observe a rearrangement within the coordination sphere leading to movement of Cu(2+) to the center of the peptide ring with concurrent coordination of four nitrogen donors. Spin-lattice relaxation enhancements and potentiometric measurements clearly indicate that deprotonated amide nitrogen atom from the β-ureidodehydroalanine moiety is the fourth donor atom.
authors: Faculty of Chemistry, University of Wrocław, Wrocław, Poland.
authors: Kamila
authors: K
authors: Stokowa
authors: Wojciech
authors: W
authors: Szczepanik
authors: Nicola
authors: N
authors: Gaggelli
authors: Elena
authors: E
authors: Gaggelli
authors: Gianni
authors: G
authors: Valensin
authors: Małgorzata
authors: M
authors: Jeżowska-Bojczuk
mesh_terms: D000904:Antibiotics, Antitubercular / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002207:Capreomycin / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011199:Potentiometry; D011485:Protein Binding; D013053:Spectrophotometry; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D000904:Antibiotics, Antitubercular; D010455:Peptides; D002207:Capreomycin; D015091:beta-Alanine; D003300:Copper; C011757:2,3-diaminopropionic acid