Clostridial collagenases are among the most efficient degraders of eukaryotic collagen known; saprophytes use collagen as a carbon source while pathogens additionally digest collagen to aid in host colonization. Has both tripeptidylcarboxypeptidase on Gly-X-Y and endopeptidase activities; the endopeptidase cuts within the triple helix region of collagen while tripeptidylcarboxypeptidase successively digests the exposed ends, thus clostridial collagenases can digest large sections of collagen (PubMed:3002446). The full-length protein has collagenase activity, while both the 116 kDa and 98 kDa forms act on gelatin (PubMed:7961400). In vitro digestion of soluble calf skin collagen fibrils requires both ColG and ColH; ColG forms missing the second collagen-binding domain is also synergistic with ColH, although their overall efficiency is decreased (PubMed:18374061, PubMed:22099748). Digestion of collagen requires Ca(2+) and is inhibited by EDTA (PubMed:9452493). The activator domain (residues 119-388) and catalytic subdomain (330-601) open and close around substrate allowing digestion when the protein is closed (PubMed:23703618). Digestion of native collagen in the triple helical region at Xaa-|-Gly bonds. With synthetic peptides, a preference is shown for Gly at P3 and P1', Pro and Ala at P2 and P2', and hydroxyproline, Ala or Arg at P3'. Binds about 5 Ca(2+) per subunit (PubMed:6087888). The metallopeptidase and PKD domains each bind 1 Ca(2+), while CDB binds 2 (PubMed:23144249, PubMed:23703618, PubMed:25760606, PubMed:28820255). The protein is less elongated in the presence of EGTA (which chelates Ca(2+)) (PubMed:23561530). Binds 1 Zn(2+) per subunit (PubMed:6087888, PubMed:10217773, PubMed:23703618, PubMed:28820255). A fourth ligand (Asp-421) not found in paralogs ColG and ColT is seen in the absence of inhibitor, which probably plays a role in substrate selection (PubMed:23703618). In the crystal with the N-aryl mercaptoacetamide-based inhibitor Zn is ligated only by the thiolate of the inhibitor (PubMed:28820255). Inhibited by EDTA (PubMed:9452493). Inhibited by 1-10-phenanthroline (PubMed:18937627). Inhibited by broad-spectrum zinc metalloprotease inhibitor batimastat (PubMed:28820255). N-aryl mercaptoacetamide-based inhibitors have been isolated that act on clostridial collagenases with submicromolar affinity while having negligibile activity on human collagenases (PubMed:28820255). kcat is 0.11 per second on Pz peptide with whole enzyme (PubMed:10217773). kcat is 15.9 per second on FALGPA with a catalytic fragment (residues 41-717) (PubMed:18937627). The mature protein has 4 domains; a metalloprotease domain (S1, approximately residues 41-717), S2a (718-810, equivalent to PKD 1), S2b (811-904, equivalent to PKD 2) and a collagen-binding domain (S3, 905-1021) (PubMed:9922257, PubMed:9452493). The protein has an elongated shape, which lengthens further in calcium-chelated conditions; calcium-chelation also increases its susceptibility to exogenous proteases (PubMed:23561530). The S1 domain has the collagen hydrolytic activity (PubMed:9452493, PubMed:18937627). The metalloprotease S1 domain is composed of 3 subdomains which together resemble a saddle; an activator domain (residues 41-320), the catalytic peptidase subdomain (330-601) and a helper subdomain (609-721) (PubMed:23703618). Unlike the S2 domain in ColG, upon binding to Ca(2+) the midsections of S2a and S2b remain rigid; Ca(2+) binding confers thermostability (PubMed:25760606). Ca(2+)-binding also alters the orientation of the N-terminal linker of S2b so it lies along the long axis of the domain (PubMed:25760606). S3 has collagen-binding activity (PubMed:9452493). The structure of S3 becomes more thermostable when it is bound to Ca(2+) (PubMed:23144249). Isolated CBD S3 binds unidirectionally to the C-terminus of the collagen triple helix via a surface cleft (PubMed:23144249). Upon purification gives rise to 98 kDa, 105 kDa and 116 kDa (full-length) proteins, all of which have the same N-terminus (PubMed:7961400, PubMed:9922257). Widely used for tissue dissociation due to its potent activity on connective tissue. A mix of ColG and ColH is used for isolation of pancreatic islet cells for subsequent transplantation. A mix of ColG and ColH has been used to allow release of retained placenta in cows and mares, and its use in humans has been proposed. Has been used to anchor otherwise diffusible proteins to the host extracellular matrix. Fusions between the collagen-binding domain (S2B plus S3) and rat epidermal growth factor or human basic fibroblast growth factor (bFGF) were injected subcutaneously into adult male BALB/c-nu mice. The fusion proteins remained at the sites of injection for up to 10 days, and bFGF strongly stimulated fibroblast growth (PubMed:9618531). N-aryl mercaptoacetamide-based inhibitors with submicromolar affinity for clostridial collagenases but negligibile activity on human collagenases have been discovered that may lead to promising anti-infective drugs against Clostridia (PubMed:28820255). SANTYL Ointment (Smith and Nephew, Inc.) is indicated for debriding chronic dermal ulcers and severely burned areas. It is unclear which of the collagenases from this bacteria is in the ointment. Xiaflex (Endo Pharmaceuticals, Inc.) is a mix of H.histolytica collagenases (ColG and ColH) used to treat both Dupuytren disease and Peyronie disease. Dupuytren disease is a progressive genetic disorder of pathologic collagen production and deposition under the skin of the hand that causes the fingers to be drawn into the palm, leading to flexion contractures of the joints, which can severely limit hand function. Injections of collagenase may reduce these joint contractures (PubMed:19726771, PubMed:10913202). Peyronie disease (PD) is characterized by a disorganized, excessive deposition of collagen that forms a plaque within the penis. The plaque restricts lengthening on the affected side during erection, which can lead to penile curvature deformity, discomfort and erectile dysfunction, and can eventually lead to psychosocial effects such as depression and relationship difficulties. Studies have shown the clinical efficacy of collagenase injection for reducing penile curvature deformity and PD symptom bother (PubMed:8417217, PubMed:25711400). Clostridial collagenases enable the bacteria to infiltrate and colonize host tissue, and contribute to gas gangrene (myonecrosis) pathogenesis. Belongs to the peptidase M9B family. Collagenase subfamily.