6r5b - Revision history

OCA at 12:15, 24 January 2024

OCA — Wed, 24 Jan 2024 12:15:31 GMT

←Older revision		Revision as of 12:15, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6r5b' size='340' side='right'caption='[[6r5b]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='6r5b' size='340' side='right'caption='[[6r5b]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6r5b]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_difficilis"_hall_and_o'toole_1935 "bacillus difficilis" hall and o'toole 1935~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R5B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6R5B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6r5b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R5B FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=ACE:ACETYL+GROUP'>ACE</scene~~>, ~~<scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</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]] 2.06Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>zmp1, ppep-1, CD630_28300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~1496~~ "~~Bacillus difficilis~~" ~~Hall and O'Toole 1935])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[http://en.wikipedia.org/wiki/Pro-Pro_endopeptidase Pro-Pro endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.89 3.4.24.89]~~ </~~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=6r5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r5b OCA], [https://pdbe.org/6r5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r5b RCSB], [https://www.ebi.ac.uk/pdbsum/6r5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r5b ProSAT]</span></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=6r5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r5b OCA], [~~http~~://pdbe.org/6r5b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6r5b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6r5b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6r5b ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~PPEP1_PEPD6 PPEP1_PEPD6]~~] Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin.<ref>PMID:24303041</ref> <ref>PMID:24623589</ref> <ref>PMID:26283789</ref> <ref>PMID:26522134</ref>	+	[https://www.uniprot.org/uniprot/PPEP1_CLOD6 PPEP1_CLOD6] Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin.<ref>PMID:24303041</ref> <ref>PMID:24623589</ref> <ref>PMID:26283789</ref> <ref>PMID:26522134</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus difficilis hall and o'toole 1935~~]]	+	[[Category: Clostridioides difficile]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Pro-Pro endopeptidase]]~~	+	[[Category: Baumann U]]
-	[[Category: Baumann, U]]	+	[[Category: Pichlo C]]
-	[[Category: Pichlo, C]]	+	[[Category: Wojtalla F]]
-	[[Category: Wojtalla, F]]	+
-	~~[[Category: Clostridium difficile]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Pro-pro endopeptidase 1]]~~	+
-	~~[[Category: Virulence factor]]~~	+
-	~~[[Category: Zinc metallopeptidase~~]]	+

OCA at 06:24, 7 August 2019

OCA — Wed, 07 Aug 2019 06:24:38 GMT

←Older revision		Revision as of 06:24, 7 August 2019
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	<StructureSection load='6r5b' size='340' side='right'caption='[[6r5b]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='6r5b' size='340' side='right'caption='[[6r5b]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6r5b]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R5B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6r5b]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_difficilis"_hall_and_o'toole_1935 "bacillus difficilis" hall and o'toole 1935]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R5B FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">zmp1, ppep-1, CD630_28300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1496 "Bacillus difficilis" Hall and O'Toole 1935])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pro-Pro_endopeptidase Pro-Pro endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.89 3.4.24.89] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pro-Pro_endopeptidase Pro-Pro endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.89 3.4.24.89] </span></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=6r5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r5b OCA], [http://pdbe.org/6r5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r5b RCSB], [http://www.ebi.ac.uk/pdbsum/6r5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r5b ProSAT]</span></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=6r5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r5b OCA], [http://pdbe.org/6r5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r5b RCSB], [http://www.ebi.ac.uk/pdbsum/6r5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r5b ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus difficilis hall and o'toole 1935]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Pro-Pro endopeptidase]]		[[Category: Pro-Pro endopeptidase]]

OCA at 07:44, 26 June 2019

OCA — Wed, 26 Jun 2019 07:44:24 GMT

←Older revision		Revision as of 07:44, 26 June 2019
Line 10:		Line 10:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PPEP1_PEPD6 PPEP1_PEPD6]] Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin.<ref>PMID:24303041</ref> <ref>PMID:24623589</ref> <ref>PMID:26283789</ref> <ref>PMID:26522134</ref>		[[http://www.uniprot.org/uniprot/PPEP1_PEPD6 PPEP1_PEPD6]] Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin.<ref>PMID:24303041</ref> <ref>PMID:24623589</ref> <ref>PMID:26283789</ref> <ref>PMID:26522134</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Pro-Pro endopeptidase-1 (PPEP-1) is a secreted metalloprotease from the bacterial pathogen Clostridium difficile that cleaves two endogenous adhesion proteins. PPEP-1 is therefore important for bacterial motility and hence for efficient gut colonization during infection. PPEP-1 exhibits a unique specificity for Pro-Pro peptide bonds within the consensus sequence VNP downward arrowPVP. In this study, we combined information from crystal and NMR structures with mutagenesis and enzyme kinetics to investigate the mechanism and substrate specificity of PPEP-1. Our analyses revealed that the substrate-binding cleft of PPEP-1 is shaped complementary to the major conformation of the substrate in solution. We found that it possesses features that accept a tertiary amide and help discriminate P1' residues by their amide hydrogen bond-donating potential. We also noted that residues Lys-101, Trp-103, and Glu-184 are crucial for proteolytic activity. Upon substrate binding, these residues position a flexible loop over the substrate-binding cleft and modulate the second coordination sphere of the catalytic zinc ion. On the basis of these findings, we propose an induced-fit model in which pre-structured substrates are recognized, followed by substrate positioning within the active-site cleft and a concomitant increase in the Lewis acidity of the catalytic Zn2+ ion. In conclusion, our findings provide detailed structural and mechanistic insights into the substrate recognition and specificity of PPEP-1 from the common gut pathogen Clostridium difficile.
		+
		+	Molecular determinants of the mechanism and substrate specificity of Clostridium difficile proline-proline endopeptidase-1.,Pichlo C, Juetten L, Wojtalla F, Schacherl M, Diaz D, Baumann U J Biol Chem. 2019 Jun 10. pii: RA119.009029. doi: 10.1074/jbc.RA119.009029. PMID:31182482<ref>PMID:31182482</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6r5b" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:50, 12 June 2019

OCA — Wed, 12 Jun 2019 05:50:47 GMT

←Older revision		Revision as of 05:50, 12 June 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6r5b is ON HOLD~~	+	==Crystal structure of PPEP-1(W103H/E143A/Y178F) in complex with substrate peptide Ac-EVNPPVP-CONH2==
-		+	<StructureSection load='6r5b' size='340' side='right'caption='[[6r5b]], [[Resolution\|resolution]] 2.06Å' scene=''>
-	~~Authors: Pichlo, C., Wojtalla, F., Baumann, U.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6r5b]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R5B FirstGlance]. <br>
-	~~Description:~~ Crystal structure of PPEP-1(W103H/E143A/Y178F) in complex with substrate peptide Ac-EVNPPVP-CONH2	+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pro-Pro_endopeptidase Pro-Pro endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.89 3.4.24.89] </span></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=6r5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r5b OCA], [http://pdbe.org/6r5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r5b RCSB], [http://www.ebi.ac.uk/pdbsum/6r5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r5b ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PPEP1_PEPD6 PPEP1_PEPD6]] Zinc-dependent endoprotease with a unique preference for proline residues surrounding the scissile bond. Exhibits a high preference for an asparagine at the P2 position and hydrophobic residues (Val, Ile, Leu) at the P3 position. Efficiently cleaves the LPXTG cell surface proteins CD630_28310 and CD630_32460 at multiple cleavage sites in vivo. Has a role in the regulation of C.difficile adhesion versus motility by cleaving surface adhesion proteins such as the collagen binding protein CD630_28310, and is important for efficient infection. Is also able to cleave fibronectin and fibrinogen in vitro; cleaves at the N-terminus of the beta-chain of fibrinogen. Destabilizes the fibronectin network produced by human fibroblasts. Therefore, may be important in key steps of clostridial pathogenesis by degrading extracellular matrix components associated with the gut epithelial cells. To a lesser extent, IgA1, IgA2, and human HSP 90-beta, but not HSP 90-alpha, are also substrates for the enzyme. Is not active on different collagen types, casein and gelatin.<ref>PMID:24303041</ref> <ref>PMID:24623589</ref> <ref>PMID:26283789</ref> <ref>PMID:26522134</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Pro-Pro endopeptidase]]
		+	[[Category: Baumann, U]]
	[[Category: Pichlo, C]]		[[Category: Pichlo, C]]
-	[[Category: Baumann, U]]
	[[Category: Wojtalla, F]]		[[Category: Wojtalla, F]]
		+	[[Category: Clostridium difficile]]
		+	[[Category: Hydrolase]]
		+	[[Category: Pro-pro endopeptidase 1]]
		+	[[Category: Virulence factor]]
		+	[[Category: Zinc metallopeptidase]]

OCA: Protected "6r5b" [edit=sysop:move=sysop]

OCA — Wed, 03 Apr 2019 04:58:10 GMT

Protected "6r5b" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:58, 3 April 2019

OCA: New page: '''Unreleased structure''' The entry 6r5b is ON HOLD Authors: Pichlo, C., Wojtalla, F., Baumann, U. Description: Crystal structure of PPEP-1(W103H/E143A/Y178F) in complex with substrat...

OCA — Wed, 03 Apr 2019 04:58:08 GMT

New page: '''Unreleased structure''' The entry 6r5b is ON HOLD Authors: Pichlo, C., Wojtalla, F., Baumann, U. Description: Crystal structure of PPEP-1(W103H/E143A/Y178F) in complex with substrat...

New page

'''Unreleased structure'''

The entry 6r5b is ON HOLD

Authors: Pichlo, C., Wojtalla, F., Baumann, U.

Description: Crystal structure of PPEP-1(W103H/E143A/Y178F) in complex with substrate peptide Ac-EVNPPVP-CONH2
[[Category: Unreleased Structures]]
[[Category: Pichlo, C]]
[[Category: Baumann, U]]
[[Category: Wojtalla, F]]