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4tn9

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Current revision

Crystal structure of Clostridium histolyticum ColG collagenase polycystic kidney disease-like domain at 1.4 Angstrom resolution

Structural highlights

4tn9 is a 2 chain structure with sequence from Hathewaya histolytica. This structure supersedes the now removed PDB entry 3jqu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COLG_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). Active on soluble type I collagen, insoluble collagen, azocoll, soluble PZ-peptide (all collagenase substrates) and gelatin (PubMed:9922257). The full-length protein has collagenase activity, while the in vivo derived C-terminally truncated shorter versions only act on gelatin (PubMed:9922257). In vitro digestion of soluble calf skin collagen fibrils requires both ColG and ColH; ColG forms missing the second collagen-binding domain are also synergistic with ColH, although their overall efficiency is decreased (PubMed:18374061, PubMed:22099748). The activator domain (residues 119-388) and catalytic subdomain (389-670) open and close around substrate using a Gly-rich hinge (387-397), allowing digestion when the protein is closed (PubMed:21947205, PubMed:23703618). Binding of collagen requires Ca(2+) and is inhibited by EGTA; the collagen-binding domain (CBD, S3a plus S3b) specifically recognizes the triple-helical conformation made by 3 collagen protein chains in the triple-helical region (PubMed:11121400). Isolated CBD (S3a plus S3b) binds collagen fibrils and sheets of many tissues (PubMed:11913772).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11]

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^[12]

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

References

↑ Matsushita O, Koide T, Kobayashi R, Nagata K, Okabe A. Substrate recognition by the collagen-binding domain of Clostridium histolyticum class I collagenase. J Biol Chem. 2001 Mar 23;276(12):8761-70. doi: 10.1074/jbc.M003450200. Epub 2000 , Dec 19. PMID:11121400 doi:http://dx.doi.org/10.1074/jbc.M003450200
↑ Toyoshima T, Matsushita O, Minami J, Nishi N, Okabe A, Itano T. Collagen-binding domain of a Clostridium histolyticum collagenase exhibits a broad substrate spectrum both in vitro and in vivo. Connect Tissue Res. 2001;42(4):281-90. doi: 10.3109/03008200109016842. PMID:11913772 doi:http://dx.doi.org/10.3109/03008200109016842
↑ 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
↑ Eckhard U, Schonauer E, Nuss D, Brandstetter H. Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis. Nat Struct Mol Biol. 2011 Sep 25;18(10):1109-14. doi: 10.1038/nsmb.2127. PMID:21947205 doi:10.1038/nsmb.2127
↑ 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
↑ Matsushita O, Jung CM, Katayama S, Minami J, Takahashi Y, Okabe A. Gene duplication and multiplicity of collagenases in Clostridium histolyticum. J Bacteriol. 1999 Feb;181(3):923-33. doi: 10.1128/JB.181.3.923-933.1999. PMID:9922257 doi:http://dx.doi.org/10.1128/JB.181.3.923-933.1999
↑ 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/4tn9"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Clostridium histolyticum ColG collagenase polycystic kidney disease-like domain at 1.4 Angstrom resolution==
-<StructureSection load='4tn9' size='340' side='right' caption='[[4tn9]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+<StructureSection load='4tn9' size='340' side='right'caption='[[4tn9]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4tn9]] is a 2 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3jqu 3jqu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TN9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TN9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4tn9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hathewaya_histolytica Hathewaya histolytica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3jqu 3jqu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TN9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TN9 FirstGlance]. <br>
-</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=4tn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tn9 OCA], [http://pdbe.org/4tn9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tn9 RCSB], [http://www.ebi.ac.uk/pdbsum/4tn9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tn9 ProSAT]</span></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]] 1.4&#8491;</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=4tn9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tn9 OCA], [https://pdbe.org/4tn9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tn9 RCSB], [https://www.ebi.ac.uk/pdbsum/4tn9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tn9 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/COLG_HATHI COLG_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). Active on soluble type I collagen, insoluble collagen, azocoll, soluble PZ-peptide (all collagenase substrates) and gelatin (PubMed:9922257). The full-length protein has collagenase activity, while the in vivo derived C-terminally truncated shorter versions only act on gelatin (PubMed:9922257). In vitro digestion of soluble calf skin collagen fibrils requires both ColG and ColH; ColG forms missing the second collagen-binding domain are also synergistic with ColH, although their overall efficiency is decreased (PubMed:18374061, PubMed:22099748). The activator domain (residues 119-388) and catalytic subdomain (389-670) open and close around substrate using a Gly-rich hinge (387-397), allowing digestion when the protein is closed (PubMed:21947205, PubMed:23703618). Binding of collagen requires Ca(2+) and is inhibited by EGTA; the collagen-binding domain (CBD, S3a plus S3b) specifically recognizes the triple-helical conformation made by 3 collagen protein chains in the triple-helical region (PubMed:11121400). Isolated CBD (S3a plus S3b) binds collagen fibrils and sheets of many tissues (PubMed:11913772).<ref>PMID:11121400</ref> <ref>PMID:11913772</ref> <ref>PMID:18374061</ref> <ref>PMID:18937627</ref> <ref>PMID:21947205</ref> <ref>PMID:22099748</ref> <ref>PMID:23703618</ref> <ref>PMID:24125730</ref> <ref>PMID:28820255</ref> <ref>PMID:3002446</ref> <ref>PMID:9922257</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 17: / Line 20: @@
 ==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: Gann, S]]
+[[Category: Large Structures]]
-[[Category: Matsushita, O]]
+[[Category: Bauer R]]
-[[Category: Philominathan, S T.L]]
+[[Category: Gann S]]
-[[Category: Sakon, J]]
+[[Category: Matsushita O]]
-[[Category: Metal binding protein]]
+[[Category: Philominathan STL]]
+[[Category: Sakon J]]

4tn9

From Proteopedia

Current revision

Crystal structure of Clostridium histolyticum ColG collagenase polycystic kidney disease-like domain at 1.4 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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