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Recognition and catabolism of synthetic heterotrimeric collagen peptides by matrix metalloproteinases
- Source :
- Chemistry & Biology. 7(2):119-132
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- Background: The general consensus is that interstitial collagens are digested by collagenases and denatured collagen by gelatinases, although processing of fibrillar and acetic-acid-soluble collagen by gelatinase A has also been reported. One of the main difficulties in studying the mechanism of action of these matrix metalloproteinases (MMPs) derives from the physicochemical properties of the natural triple-helical collagen, which makes it difficult to handle. Results: Synthetic heterotrimeric collagenous peptides that contain the collagenase cleavage site of human collagen type I and differ in the thermal stability of the triple-helical fold were used to mimic natural collagen and gelatin, respectively. Results from digestion of these substrates by fibroblast and neutrophil collagenases (MMP-1 and MMP-8), as well as by gelatinase A (MMP-2), confirmed that the two classes of enzymes operate within the context of strong conformational dependency of the substrates. It was also found that gelatinases and collagenases exhibit two distinct proteolytic mechanisms: gelatinase digests the gelatin-like heterotrimer rapidly in individual steps with intermediate releases of partially processed substrate into the medium, whereas collagenases degrade the triple-helical heterotrimer by trapping it until scission through all three α chains is achieved. Conclusions: The results confirm the usefulness of synthetic heterotrimeric collagenous peptides in the folded and unfolded state as mimics of the natural substrates collagen and gelatin, respectively, to gain a better a insight into the proteolytic mechanisms of matrix metalloproteinases.
- Subjects :
- Models, Molecular
Gelatinases
food.ingredient
Gelatinase A
Clinical Biochemistry
Biology
Matrix metalloproteinase
digestion
010402 general chemistry
01 natural sciences
Gelatin
Biochemistry
Substrate Specificity
03 medical and health sciences
food
Heterotrimeric G protein
Drug Discovery
medicine
Humans
Gelatinase
Fibroblast
Molecular Biology
Chromatography, High Pressure Liquid
030304 developmental biology
Pharmacology
0303 health sciences
mechanisms
Binding Sites
heterotrimeric substrates
General Medicine
Surface Plasmon Resonance
Synthetic heterotrimeric substrates
Matrix Metalloproteinases
Protein Structure, Tertiary
0104 chemical sciences
Kinetics
Matrix Metalloproteinase 8
medicine.anatomical_structure
synthetic
Collagenase
Matrix Metalloproteinase 2
Molecular Medicine
Collagen
MMPs
Matrix Metalloproteinase 1
Peptides
collagenous peptides
medicine.drug
Subjects
Details
- ISSN :
- 10745521
- Volume :
- 7
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Chemistry & Biology
- Accession number :
- edsair.doi.dedup.....ffdb6552abbae4d2ecd7155b9eb1b413
- Full Text :
- https://doi.org/10.1016/s1074-5521(00)00077-6