title: Copper(II) interaction with peptide fragments of histidine-proline-rich glycoprotein: Speciation, stability and binding details.
abstract: GHHPH is the peptide repeat present in histidine-proline rich glycoprotein (HPRG), a plasma glycoprotein involved in angiogenesis process. The copper(II) ions interaction with mono (Ac-GHHPHG-NH(2)) and its bis-repeat (Ac-GHHPHGHHPHG-NH(2)) was investigated by means of potentiometric and spectroscopic techniques. To single out the copper(II) coordination environments of different species formed with Ac-GHHPHG-NH(2), three single point mutated peptides were also synthesized and their ability to coordinate Cu(2+) investigated. Ac-GHHPHG-NH(2) binds Cu(2+) by the imidazole side chain and the amide nitrogen deprotonation that takes place towards the N-terminus. The bis-repeat is able to bind Cu(2+) more efficiently than Ac-GHHPHG-NH(2). This difference is not only due to the number of His residues in the sequence but also to the different binding sites. In fact, the comparison of the potentiometric and spectroscopic data of the copper(II) complexes with a bis-repeatPeg construct Ac-(GHHPHG)-Peg-(GHHPHG)-NH(2) and those of the metal complexes with Ac-HGHH-NH(2), indicates that the central HGHH amino acid sequence is the main copper(II) binding site.
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR-Catania, Viale A. Doria 6, Catania, Italy. dlamendo@unict.it
authors.forename: Diego
authors.initials: D
authors.lastname: La Mendola
authors.forename: Antonio
authors.initials: A
authors.lastname: Magrì
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Santoro
authors.forename: Vincenzo G
authors.initials: VG
authors.lastname: Nicoletti
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D011199:Potentiometry; D011392:Proline / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013053:Spectrophotometry; D000099053:Histidine-Rich Glycoprotein
chemical_list: D056831:Coordination Complexes; D006023:Glycoproteins; D010446:Peptide Fragments; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D003300:Copper; D011392:Proline