6btn - Revision history

OCA at 08:52, 11 November 2020

2020-11-11T08:52:11Z

←Older revision		Revision as of 08:52, 11 November 2020
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	==BMP1 complexed with a reverse hydroxymate - compound 1==		==BMP1 complexed with a reverse hydroxymate - compound 1==
-	<StructureSection load='6btn' size='340' side='right' caption='[[6btn]], [[Resolution\|resolution]] 2.05Å' scene=''>	+	<StructureSection load='6btn' size='340' side='right'caption='[[6btn]], [[Resolution\|resolution]] 2.05Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6btn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BTN OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BTN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6btn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BTN OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BTN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E8M:(3S)-6-cyclohexyl-3-{3-[(dimethylamino)methyl]-1,2,4-oxadiazol-5-yl}-N-hydroxyhexanamide'>E8M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E8M:(3S)-6-cyclohexyl-3-{3-[(dimethylamino)methyl]-1,2,4-oxadiazol-5-yl}-N-hydroxyhexanamide'>E8M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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></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></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Procollagen_C-endopeptidase Procollagen C-endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.19 3.4.24.19] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Procollagen_C-endopeptidase Procollagen C-endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.19 3.4.24.19] </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=6btn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6btn OCA], [http://pdbe.org/6btn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6btn RCSB], [http://www.ebi.ac.uk/pdbsum/6btn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6btn ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6btn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6btn OCA], [http://pdbe.org/6btn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6btn RCSB], [http://www.ebi.ac.uk/pdbsum/6btn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6btn ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 6btn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6btn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bone morphogenetic protein 3D structures\|Bone morphogenetic protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Procollagen C-endopeptidase]]		[[Category: Procollagen C-endopeptidase]]
	[[Category: Gampe, R]]		[[Category: Gampe, R]]

OCA at 21:46, 9 August 2018

2018-08-09T21:46:50Z

←Older revision		Revision as of 21:46, 9 August 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6btn is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==BMP1 complexed with a reverse hydroxymate - compound 1==
		+	<StructureSection load='6btn' size='340' side='right' caption='[[6btn]], [[Resolution\|resolution]] 2.05Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6btn]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BTN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BTN FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E8M:(3S)-6-cyclohexyl-3-{3-[(dimethylamino)methyl]-1,2,4-oxadiazol-5-yl}-N-hydroxyhexanamide'>E8M</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Procollagen_C-endopeptidase Procollagen C-endopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.19 3.4.24.19] </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=6btn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6btn OCA], [http://pdbe.org/6btn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6btn RCSB], [http://www.ebi.ac.uk/pdbsum/6btn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6btn ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/BMP1_HUMAN BMP1_HUMAN]] Defects in BMP1 are the cause of osteogenesis imperfecta 13 (OI13) [MIM:[http://omim.org/entry/614856 614856]]. An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by bone fragility, low bone mass, and recurrent fractures. OI13 is characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, severe bone deformity, and recurrent fractures affecting both upper and lower limbs.<ref>PMID:22482805</ref> <ref>PMID:22052668</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BMP1_HUMAN BMP1_HUMAN]] Cleaves the C-terminal propeptides of procollagen I, II and III. Induces cartilage and bone formation. May participate in dorsoventral patterning during early development by cleaving chordin (CHRD). Responsible for the proteolytic activation of lysyl oxidase LOX.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Bone Morphogenetic Protein 1 (BMP1) inhibition is a potential method for treating fibrosis because BMP1, a member of the zinc metalloprotease family, is required to convert pro-collagen to collagen. A novel class of reverse hydroxamate BMP1 inhibitors was discovered, and cocrystal structures with BMP1 were obtained. The observed binding mode is unique in that the small molecule occupies the nonprime side of the metalloprotease pocket providing an opportunity to build in metalloprotease selectivity. Structure-guided modification of the initial hit led to the identification of an oral in vivo tool compound with selectivity over other metalloproteases. Due to irreversible inhibition of cytochrome P450 3A4 for this chemical class, the risk of potential drug-drug interactions was managed by optimizing the series for subcutaneous injection.

-	~~Authors: Gampe~~, R., ~~Shewchuk~~, L.	+	Reverse Hydroxamate Inhibitors of Bone Morphogenetic Protein 1.,Kallander LS, Washburn D, Hilfiker MA, Eidam HS, Lawhorn BG, Prendergast J, Fox R, Dowdell S, Manns S, Hoang T, Zhao S, Ye G, Hammond M, Holt DA, Roethke T, Hong X, Reid RA, Gampe R, Zhang H, Diaz E, Rendina AR, Quinn AM, Willette B ACS Med Chem Lett. 2018 Jul 2;9(7):736-740. doi: 10.1021/acsmedchemlett.8b00173. , eCollection 2018 Jul 12. PMID:30034610<ref>PMID:30034610</ref>

-	~~Description: BMP1 complexed with~~ a ~~reverse hydroxymate~~ -~~compound 1~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6btn" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Procollagen C-endopeptidase]]
	[[Category: Gampe, R]]		[[Category: Gampe, R]]
	[[Category: Shewchuk, L]]		[[Category: Shewchuk, L]]
		+	[[Category: Endopeptidase]]
		+	[[Category: Hydrolase]]

OCA at 07:10, 10 January 2018

2018-01-10T07:10:06Z

←Older revision		Revision as of 07:10, 10 January 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6btn is ON HOLD	+	The entry 6btn is ON HOLD until Paper Publication

	Authors: Gampe, R., Shewchuk, L.		Authors: Gampe, R., Shewchuk, L.

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

2017-12-13T05:57:28Z

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

←Older revision

Revision as of 05:57, 13 December 2017

OCA: New page: '''Unreleased structure''' The entry 6btn is ON HOLD Authors: Gampe, R., Shewchuk, L. Description: BMP1 complexed with a reverse hydroxymate -compound 1 [[Category: Unreleased Structur...

2017-12-13T05:57:26Z

New page: '''Unreleased structure''' The entry 6btn is ON HOLD Authors: Gampe, R., Shewchuk, L. Description: BMP1 complexed with a reverse hydroxymate -compound 1 [[Category: Unreleased Structur...

New page

'''Unreleased structure'''

The entry 6btn is ON HOLD

Authors: Gampe, R., Shewchuk, L.

Description: BMP1 complexed with a reverse hydroxymate -compound 1
[[Category: Unreleased Structures]]
[[Category: Gampe, R]]
[[Category: Shewchuk, L]]