OCA at 23:09, 27 December 2023

2023-12-27T23:09:46Z

←Older revision		Revision as of 23:09, 27 December 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~8b7h~~ is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of human Gremlin-1 in complex with Fab==
		+	<StructureSection load='8b7h' size='340' side='right'caption='[[8b7h]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8b7h]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B7H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B7H 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]] 1.95Å</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=8b7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b7h OCA], [https://pdbe.org/8b7h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b7h RCSB], [https://www.ebi.ac.uk/pdbsum/8b7h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b7h ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/GREM1_HUMAN GREM1_HUMAN] Hereditary mixed polyposis syndrome. The disease is caused by mutations affecting the gene represented in this entry. HMPS1 is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This duplication is associated with increased allele-specific GREM1 expression that may cause reduced bone morphogenetic protein (BMP) pathway activity. This mechanism also underlies tumorigenesis in juvenile polyposis of the large bowel (PubMed:22561515).<ref>PMID:22561515</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GREM1_HUMAN GREM1_HUMAN] Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner. Acts as inhibitor of monocyte chemotaxis (By similarity).<ref>PMID:10894942</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, -4, and -7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed BMP signaling, correlates with poor prognosis in a range of cancer types. A lack of published work using therapeutic modalities has precluded the testing of the hypothesis that blocking the gremlin-1/BMP interaction will provide benefits to patients. To address this shortfall, we developed ginisortamab (UCB6114), a first-in-class clinical anti-human gremlin-1 antibody, currently in clinical development for the treatment of cancer, along with its murine analog antibody Ab7326 mouse immunoglobulin G1 (mIgG1). Surface plasmon resonance assays revealed that ginisortamab and Ab7326 mIgG1 had similar affinities for human and mouse gremlin-1, with mean equilibrium dissociation constants of 87 pM and 61 pM, respectively. The gremlin-1/Ab7326 antigen-binding fragment (Fab) crystal structure revealed a gremlin-1 dimer with a Fab molecule bound to each monomer that blocked BMP binding. In cell culture experiments, ginisortamab fully blocked the activity of recombinant human gremlin-1, and restored BMP signaling pathways in human colorectal cancer (CRC) cell lines. Furthermore, in a human CRC - fibroblast co-culture system where gremlin-1 is produced by the fibroblasts, ginisortamab restored BMP signaling in both the CRC cells and fibroblasts, demonstrating its activity in a relevant human tumor microenvironment model. The safety and efficacy of ginisortamab are currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors (NCT04393298).

-	~~Authors~~:	+	Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer.,Davies GCG, Dedi N, Jones PS, Kevorkian L, McMillan D, Ottone C, Schulze MED, Scott-Tucker A, Tewari R, West S, Wright M, Rowley TF MAbs. 2023 Jan-Dec;15(1):2289681. doi: 10.1080/19420862.2023.2289681. Epub 2023 , Dec 12. PMID:38084840<ref>PMID:38084840</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8b7h" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Martinez-Fleites C]]
		+	[[Category: Schulze M-S]]

OCA at 08:40, 8 November 2023

2023-11-08T08:40:55Z

←Older revision		Revision as of 08:40, 8 November 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8b7h is ON HOLD	+	The entry 8b7h is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 10:31, 1 November 2023

2023-11-01T10:31:35Z

←Older revision		Revision as of 10:31, 1 November 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8b7h is ON HOLD ~~until Paper Publication~~	+	The entry 8b7h is ON HOLD

	Authors:		Authors:

OCA at 04:45, 9 November 2022

2022-11-09T04:45:53Z

←Older revision		Revision as of 04:45, 9 November 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8b7h is ON HOLD	+	The entry 8b7h is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8b7h" [edit=sysop:move=sysop]

2022-10-19T16:49:09Z

Protected "8b7h" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:49, 19 October 2022

OCA: New page: '''Unreleased structure''' The entry 8b7h is ON HOLD Authors: Description: Category: Unreleased Structures

2022-10-19T16:49:07Z

New page: '''Unreleased structure''' The entry 8b7h is ON HOLD Authors: Description: Category: Unreleased Structures

New page