title: Effect of Ca2+ on the secondary structure of linear and cyclic collagen sequence analogs.
abstract: To investigate the role of secondary structure in the substrate specificity of human 72 kDa type IV collagenase, we synthesised linear and cyclic collagen sequence analogs. As Ca2+ plays a crucial role in the enzyme activity, the CD and FTIR spectra of the peptides were also measured in the presence of Ca2+. Most of the linear, but none of the cyclic peptides form stable 1:1 Ca2+ complexes. The cyclic hexapeptides adopt significantly different backbone conformations comprising not only beta-turns but also the less frequent gamma-turns. Consequently, in the cyclopeptides the scissile Gly-Ile(Leu) bond is embedded into a different conformational environment, but in spite of that none of them is a substrate or an inhibitor of the enzyme. The best substrate Ac-Pro-Leu-Gly-Leu-Ala-Gly-D-Lys-OH binds Ca2+, but does not form a stable 1:1 Ca2+ complex, which suggests that instead of a folded structure an extended flexible conformation is preferred by the enzyme.
authors.affiliation: Research Group for Peptide Chemistry, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Likó
authors.forename: J
authors.initials: J
authors.lastname: Botyánszki
authors.forename: J
authors.initials: J
authors.lastname: Bódi
authors.forename: E
authors.initials: E
authors.lastname: Vass
authors.forename: Z
authors.initials: Z
authors.lastname: Majer
authors.forename: M
authors.initials: M
authors.lastname: Hollósi
authors.forename: H
authors.initials: H
authors.lastname: Süli-Vargha
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000494:pharmacology*; D002942:Circular Dichroism; D003094:Collagen / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013379:Substrate Specificity
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D002118:Calcium