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==Crystal structure of Clostridium histolyticum ColH collagenase polycystic kidney-disease-like domain 2b at 1.4 Angstrom resolution in the presence of calcium== | ==Crystal structure of Clostridium histolyticum ColH collagenase polycystic kidney-disease-like domain 2b at 1.4 Angstrom resolution in the presence of calcium== | ||
<StructureSection load='4jgu' size='340' side='right' caption='[[4jgu]], [[Resolution|resolution]] 1.42Å' scene=''> | <StructureSection load='4jgu' size='340' side='right'caption='[[4jgu]], [[Resolution|resolution]] 1.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4jgu]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4jgu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hathewaya_histolytica Hathewaya histolytica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JGU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JGU FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.42Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
< | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jgu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jgu OCA], [https://pdbe.org/4jgu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jgu RCSB], [https://www.ebi.ac.uk/pdbsum/4jgu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jgu ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/COLH_HATHI 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).<ref>PMID:18374061</ref> <ref>PMID:18937627</ref> <ref>PMID:22099748</ref> <ref>PMID:23703618</ref> <ref>PMID:24125730</ref> <ref>PMID:28820255</ref> <ref>PMID:3002446</ref> <ref>PMID:7961400</ref> <ref>PMID:9452493</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca(2+)-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)-bound holo s2b (1.4 A resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 A resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 A resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 A resolution, R = 16.9%, Rfree = 21.2%; 1.6 A resolution, R = 16.2%, Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved beta-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent beta-strand. This beta-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca(2+) the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+), but also position the Ca(2+)-interacting water molecule. Ca(2+) aligns the N-terminal linker approximately parallel to the major axis of the domain. Ca(2+) binding also increases stability against heat and guanidine hydrochloride, and may improve the longevity in the extracellular matrix. The results of this study will further assist in developing collagen-targeting vehicles for various signal molecules. | |||
Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.,Bauer R, Janowska K, Taylor K, Jordan B, Gann S, Janowski T, Latimer EC, Matsushita O, Sakon J Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):565-77. doi:, 10.1107/S1399004714027722. Epub 2015 Feb 26. PMID:25760606<ref>PMID:25760606</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4jgu" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Collagenase | *[[Collagenase 3D structures|Collagenase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Hathewaya histolytica]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bauer R]] | ||
[[Category: | [[Category: Matsushita O]] | ||
[[Category: | [[Category: Sakon J]] | ||
Latest revision as of 17:23, 8 November 2023
Crystal structure of Clostridium histolyticum ColH collagenase polycystic kidney-disease-like domain 2b at 1.4 Angstrom resolution in the presence of calciumCrystal structure of Clostridium histolyticum ColH collagenase polycystic kidney-disease-like domain 2b at 1.4 Angstrom resolution in the presence of calcium
Structural highlights
FunctionCOLH_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).[1] [2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedClostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca(2+)-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)-bound holo s2b (1.4 A resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 A resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 A resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 A resolution, R = 16.9%, Rfree = 21.2%; 1.6 A resolution, R = 16.2%, Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved beta-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent beta-strand. This beta-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca(2+) the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+), but also position the Ca(2+)-interacting water molecule. Ca(2+) aligns the N-terminal linker approximately parallel to the major axis of the domain. Ca(2+) binding also increases stability against heat and guanidine hydrochloride, and may improve the longevity in the extracellular matrix. The results of this study will further assist in developing collagen-targeting vehicles for various signal molecules. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.,Bauer R, Janowska K, Taylor K, Jordan B, Gann S, Janowski T, Latimer EC, Matsushita O, Sakon J Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):565-77. doi:, 10.1107/S1399004714027722. Epub 2015 Feb 26. PMID:25760606[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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