This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4u6t

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal structure of the Clostridium histolyticum colH collagenase polycystic kidney disease-like domain 2a at 1.76 Angstrom resolution

Structural highlights

4u6t is a 4 chain structure with sequence from Hathewaya histolytica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.76Å
Ligands:
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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

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^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McCarthy RC, Spurlin B, Wright MJ, Breite AG, Sturdevant LK, Dwulet CS, Dwulet FE. Development and characterization of a collagen degradation assay to assess purified collagenase used in islet isolation. Transplant Proc. 2008 Mar;40(2):339-42. doi: 10.1016/j.transproceed.2008.01.041. PMID:18374061 doi:http://dx.doi.org/10.1016/j.transproceed.2008.01.041
↑ Eckhard U, Schonauer E, Ducka P, Briza P, Nuss D, Brandstetter H. Biochemical characterization of the catalytic domains of three different Clostridial collagenases. Biol Chem. 2009 Jan;390(1):11-8. doi: 10.1515/BC.2009.004. PMID:18937627 doi:http://dx.doi.org/10.1515/BC.2009.004
↑ Breite AG, McCarthy RC, Dwulet FE. Characterization and functional assessment of Clostridium histolyticum class I (C1) collagenases and the synergistic degradation of native collagen in enzyme mixtures containing class II (C2) collagenase. Transplant Proc. 2011 Nov;43(9):3171-5. doi: 10.1016/j.transproceed.2011.09.059. PMID:22099748 doi:http://dx.doi.org/10.1016/j.transproceed.2011.09.059
↑ Eckhard U, Schonauer E, Brandstetter H. Structural basis for activity regulation and substrate preference of clostridial collagenases G, H, and T. J Biol Chem. 2013 May 23. PMID:23703618 doi:10.1074/jbc.M112.448548
↑ Eckhard U, Huesgen PF, Brandstetter H, Overall CM. Proteomic protease specificity profiling of clostridial collagenases reveals their intrinsic nature as dedicated degraders of collagen. J Proteomics. 2014 Apr 4;100:102-14. doi: 10.1016/j.jprot.2013.10.004. Epub 2013 , Oct 11. PMID:24125730 doi:http://dx.doi.org/10.1016/j.jprot.2013.10.004
↑ Schonauer E, Kany AM, Haupenthal J, Husecken K, Hoppe IJ, Voos K, Yahiaoui S, Elsasser B, Ducho C, Brandstetter H, Hartmann RW. Discovery of a Potent Inhibitor Class with High Selectivity toward Clostridial Collagenases. J Am Chem Soc. 2017 Sep 13;139(36):12696-12703. doi: 10.1021/jacs.7b06935. Epub, 2017 Aug 31. PMID:28820255 doi:http://dx.doi.org/10.1021/jacs.7b06935
↑ Mookhtiar KA, Steinbrink DR, Van Wart HE. Mode of hydrolysis of collagen-like peptides by class I and class II Clostridium histolyticum collagenases: evidence for both endopeptidase and tripeptidylcarboxypeptidase activities. Biochemistry. 1985 Nov 5;24(23):6527-33. doi: 10.1021/bi00344a033. PMID:3002446 doi:http://dx.doi.org/10.1021/bi00344a033
↑ Yoshihara K, Matsushita O, Minami J, Okabe A. Cloning and nucleotide sequence analysis of the colH gene from Clostridium histolyticum encoding a collagenase and a gelatinase. J Bacteriol. 1994 Nov;176(21):6489-96. doi: 10.1128/jb.176.21.6489-6496.1994. PMID:7961400 doi:http://dx.doi.org/10.1128/jb.176.21.6489-6496.1994
↑ Matsushita O, Jung CM, Minami J, Katayama S, Nishi N, Okabe A. A study of the collagen-binding domain of a 116-kDa Clostridium histolyticum collagenase. J Biol Chem. 1998 Feb 6;273(6):3643-8. doi: 10.1074/jbc.273.6.3643. PMID:9452493 doi:http://dx.doi.org/10.1074/jbc.273.6.3643
↑ Bauer R, Janowska K, Taylor K, Jordan B, Gann S, Janowski T, Latimer EC, Matsushita O, Sakon J. Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH. Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):565-77. doi:, 10.1107/S1399004714027722. Epub 2015 Feb 26. PMID:25760606 doi:http://dx.doi.org/10.1107/S1399004714027722

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4u6t"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Clostridium histolyticum colH collagenase polycystic kidney disease-like domain 2a at 1.76 Angstrom resolution==
-<StructureSection load='4u6t' size='340' side='right' caption='[[4u6t]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
+<StructureSection load='4u6t' size='340' side='right'caption='[[4u6t]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u6t]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U6T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u6t]] is a 4 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=4U6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U6T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u7k|4u7k]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u6t RCSB], [http://www.ebi.ac.uk/pdbsum/4u6t PDBsum]</span></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=4u6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u6t OCA], [https://pdbe.org/4u6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u6t RCSB], [https://www.ebi.ac.uk/pdbsum/4u6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u6t ProSAT]</span></td></tr>
 </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 ==
@@ Line 15: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4u6t" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Collagenase (non-MMP)|Collagenase (non-MMP)]]
+*[[Collagenase 3D structures|Collagenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bauer, R]]
+[[Category: Hathewaya histolytica]]
-[[Category: Janowska, K]]
+[[Category: Large Structures]]
-[[Category: Latimer, E]]
+[[Category: Bauer R]]
-[[Category: Matsushita, O]]
+[[Category: Janowska K]]
-[[Category: Sakon, J]]
+[[Category: Latimer E]]
-[[Category: Calcium-binding protein]]
+[[Category: Matsushita O]]
-[[Category: Hydrolase]]
+[[Category: Sakon J]]

4u6t

From Proteopedia

Current revision

Crystal structure of the Clostridium histolyticum colH collagenase polycystic kidney disease-like domain 2a at 1.76 Angstrom resolution

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox