Structural properties of a collagenous heterotrimer that mimics the collagenase cleavage site of collagen type I.
Collagens contain sequence- and conformation-dependent epitopes responsible for their digestion by collagenases at specific loci. A synthetic heterotrimer construct containing the collagenase cleavage site of collagen type I was found to mimic perfectly native collagen in terms of selectivity and mode of enzymatic degradation. The NMR conformational analysis of this molecule clearly revealed the presence of two structural domains, i.e. a triple helix spanning the Gly-Pro-Hyp repeats and a less ordered portion corresponding to the collagenase cleavage site where the three chains are aligned in extended conformation with loose interchain contacts. These structural properties allow for additional insights into the very particular mechanism of collagen digestion by collagenases.
Fiori
Stella
S
Max-Planck-Institut für Biochemie, AG Bioorganische Chemie, Am Klopferspitz 18a, 82152 Martinsried, Germany.
Saccà
Barbara
B
Moroder
Luis
L
D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D024042:Collagen Type I / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011522:Protons; D013379:Substrate Specificity; D013816:Thermodynamics
D024042:Collagen Type I; D010446:Peptide Fragments; D011522:Protons; D006859:Hydrogen; D017364:Collagenases