2y72: Difference between revisions

Latest revision as of 13:47, 20 December 2023

Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.

Structural highlights

2y72 is a 2 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 1.18Å
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

Collagen constitutes one-third of body protein in humans, reflecting its extensive role in health and disease. Of similar importance, therefore, are the idiosyncratic proteases that have evolved for collagen remodeling. The most efficient collagenases are those that enable clostridial bacteria to colonize their host tissues; but despite intense study, the structural and mechanistic basis of these enzymes has remained elusive. Here we present the crystal structure of collagenase G from Clostridium histolyticum at 2.55-A resolution. By combining the structural data with enzymatic and mutagenesis studies, we derive a conformational two-state model of bacterial collagenolysis, in which recognition and unraveling of collagen microfibrils into triple helices, as well as unwinding of the triple helices, are driven by collagenase opening and closing.

Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis.,Eckhard U, Schonauer E, Nuss D, Brandstetter H Nat Struct Mol Biol. 2011 Sep 25;18(10):1109-14. doi: 10.1038/nsmb.2127. PMID:21947205^[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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] 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

[9] 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

[10] 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

[11] 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

[12] 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

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@@ Line 1: / Line 1: @@
-[[Image:2y72.png|left|200px]]
-{{STRUCTURE_2y72|  PDB=2y72  |  SCENE=  }}
+==Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.==
+<StructureSection load='2y72' size='340' side='right'caption='[[2y72]], [[Resolution|resolution]] 1.18&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2y72]] 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=2Y72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y72 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.18&#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=2y72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y72 OCA], [https://pdbe.org/2y72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y72 RCSB], [https://www.ebi.ac.uk/pdbsum/2y72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y72 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 ==
+Collagen constitutes one-third of body protein in humans, reflecting its extensive role in health and disease. Of similar importance, therefore, are the idiosyncratic proteases that have evolved for collagen remodeling. The most efficient collagenases are those that enable clostridial bacteria to colonize their host tissues; but despite intense study, the structural and mechanistic basis of these enzymes has remained elusive. Here we present the crystal structure of collagenase G from Clostridium histolyticum at 2.55-A resolution. By combining the structural data with enzymatic and mutagenesis studies, we derive a conformational two-state model of bacterial collagenolysis, in which recognition and unraveling of collagen microfibrils into triple helices, as well as unwinding of the triple helices, are driven by collagenase opening and closing.
-===CRYSTAL STRUCTURE OF THE PKD DOMAIN OF COLLAGENASE G FROM CLOSTRIDIUM HISTOLYTICUM AT 1.18 ANGSTROM RESOLUTION.===
+Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis.,Eckhard U, Schonauer E, Nuss D, Brandstetter H Nat Struct Mol Biol. 2011 Sep 25;18(10):1109-14. doi: 10.1038/nsmb.2127. PMID:21947205<ref>PMID:21947205</ref>
-{{ABSTRACT_PUBMED_21947205}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2y72" style="background-color:#fffaf0;"></div>
-[[2y72]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_histolyticum Clostridium histolyticum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y72 OCA].
 ==See Also==
-*[[Collagenase (non-MMP)|Collagenase (non-MMP)]]
+*[[Collagenase 3D structures|Collagenase 3D structures]]
-*[[Tetracycline repressor protein|Tetracycline repressor protein]]
+== References ==
+<references/>
-==Reference==
+__TOC__
-<ref group="xtra">PMID:021947205</ref><ref group="xtra">PMID:021871007</ref><references group="xtra"/>
+</StructureSection>
-[[Category: Clostridium histolyticum]]
+[[Category: Hathewaya histolytica]]
-[[Category: Microbial collagenase]]
+[[Category: Large Structures]]
-[[Category: Brandstetter, H.]]
+[[Category: Brandstetter H]]
-[[Category: Eckhard, U.]]
+[[Category: Eckhard U]]
-[[Category: Beta barrel]]
-[[Category: Collagen recognition domain]]
-[[Category: Hydrolase]]
-[[Category: Polycystic kidney disease domain]]

2y72: Difference between revisions

Latest revision as of 13:47, 20 December 2023

Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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2y72: Difference between revisions

Latest revision as of 13:47, 20 December 2023

Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.Crystal structure of the PKD Domain of Collagenase G from Clostridium Histolyticum at 1.18 Angstrom Resolution.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Search