4u6t

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(Difference between revisions)

Revision as of 08:05, 22 March 2023

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.
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 3: / Line 3: @@
 <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 with sequence from [http://en.wikipedia.org/wiki/"bacillus_histolyticus"_weinberg_and_seguin_1916 "bacillus histolyticus" weinberg and seguin 1916]. 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u7k|4u7k]]</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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">colH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1498 "Bacillus histolyticus" Weinberg and Seguin 1916])</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://pdbe.org/4u6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u6t RCSB], [http://www.ebi.ac.uk/pdbsum/4u6t PDBsum], [http://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 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus histolyticus weinberg and seguin 1916]]
+[[Category: Hathewaya histolytica]]
 [[Category: Large Structures]]
-[[Category: Bauer, R]]
+[[Category: Bauer R]]
-[[Category: Janowska, K]]
+[[Category: Janowska K]]
-[[Category: Latimer, E]]
+[[Category: Latimer E]]
-[[Category: Matsushita, O]]
+[[Category: Matsushita O]]
-[[Category: Sakon, J]]
+[[Category: Sakon J]]
-[[Category: Calcium-binding protein]]
-[[Category: Hydrolase]]

4u6t

From Proteopedia

Revision as of 08:05, 22 March 2023

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?)

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