9lrm

Cryo-EM structure of collagenase H (E416Q mutant) from Hathewaya histolytica in complex with collagen model peptide (Pro-Hyp-Gly)10

spinqualitylabelsall models 9lrm, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9lrm is a 5 chain structure with sequence from Hathewaya histolytica and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: CA, HYP, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function COLH_HATHI 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). Publication Abstract from PubMed Collagen, the major structural protein in the animal extracellular matrix, forms a triple helix that resists proteolysis and requires specialised enzymes for degradation. Flesh-eating bacteria secrete collagenases that unwind the collagen triple helix and processively trim Gly-X-Y triplet repeats, yet the molecular basis of this process has remained obscure. Here, cryo-electron microscopy reveals how Hathewaya histolytica collagenase ColH engages its substrate and exploits the helix's architecture for catalysis. ColH encircles a single collagen triple helix in a closed-ring conformation and, through dynamic domain motions, dehydrates and destabilises it. The enzyme undergoes substrate-assisted twisting to adopt a rigid ratcheted conformation, in which one chain is bent into a tripeptide-long 'bight' and threaded into the active site for cleavage, while two uncut strands are partitioned to non-catalytic sites. Release of the bight appears to reset the enzyme, with the uncut strands serving as guiding tracks. Repeated cycling between dynamic and rigid states likely enables triplet-by-triplet translocation, allowing ColH to harness collagen's geometry for processive degradation. These findings reveal a bacterial strategy for collagen unwinding and cleavage distinct from that of mammalian collagenases, highlighting divergent evolutionary solutions for degrading one of nature's most intractable substrates. Bacterial collagenase harnesses collagen geometry for processive cleavage.,Oki H, Takebe K, Bonsu A, Fujii K, Masuda R, Henderson N, Mima T, Koide T, Moradi M, Matsushita O, Sakon J, Kawahara K Nat Commun. 2026 Apr 2. doi: 10.1038/s41467-026-71099-3. PMID:41927550 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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