Unlocking the Potential of Collagenases: Structures, Functions, and Emerging Therapeutic Horizons

Abstract

Collagenases, a class of enzymes that are specifically responsible for collagen degradation, have garnered substantial attention because of their pivotal roles in tissue repair, remodeling, and medical interventions. This comprehensive review investigates the diversity, structures, and mechanisms of collagenases and highlights their therapeutic potential. First, it provides an overview of the biochemical properties of collagen and highlights its importance in extracellular matrix function. Subsequently, it meticulously analyzes the sources of collagenases and their applications in tissue engineering and food processing. Notably, this review emphasizes the predominant role played by microbial collagenases in commercial settings while discussing their production and screening methods. Furthermore, this study elucidates the methodology employed for determining collagenase activity and underscores the importance of an accurate evaluation for both research purposes and clinical applications. Finally, this review highlights the future research prospects for collagenases, with a particular focus on promoting wound healing and treating scar tissue formation and fibrotic diseases.

Fig. 1.

Classification of collagenases.

Fig. 2.

Structures of MMPs, M9A, and M9B. (A) Signal peptides direct the MMP to the secretory pathway or the plasma membrane insertion pathway. The propeptide maintains the stability of the proenzyme, and when this region is removed by exogenous enzymes, the MMP proenzyme is activated. The zinc-containing catalytic active region dominates enzyme-mediated catalysis, and the hinge region connects the catalytic and hemoglobin domains. (B) Domain structures of collagenase from Vibrio parahaemolyticus. (C) Domain structures of collagenase from Vibrio alginolyticus. (D) Domain structures of collagenase from Vibrio mimicus. (E and F) Domain structures of collagenases from C. histolyticum (ColG and ColH).

Fig. 3.

Multiple sequence alignment of the catalytic center of collagenases. The left box of M9 highlights the HEXXH motif (HEXXH+E), and the right box indicates the glutamate residue. The box of the MMPs shows the zinc-binding motif HEXXHXXGXXH in the catalytic domain.

Fig. 4.

Collagenase crystal structures. (A) Ribbon representation of proMMP1. The MMP domains and inorganic ions are labeled and colored. (B) Ribbon representation of the catalytic site of proMMP1, with secondary structures colored and important segments labeled. (C) A ribbon representation of the active site of MMP1 is depicted, with the overall structure elegantly highlighted in a captivating teal hue. (D) Ribbon representation of ColG; the HEXXH zinc-binding motifs are labeled. (E) Ribbon representation of VhaC. (F) A comparison between the CM structures of VhaC (yellow) and ColG (green) is shown, and the catalytic helper subdomain of ColG is indicated by the circle.

Fig. 5.

Schematic diagram of the methods used to screen wild-type strains for collagenase production. (A) Qualitative method for screening collagenase. (B) Quantitative methods for screening collagenase.

Fig. 6.

Applications of collagenases in medical sectors.