6oml: Difference between revisions
New page: '''Unreleased structure''' The entry 6oml is ON HOLD Authors: Seeherman, H., Juo, Z.S. Description: Human BMP chimera BV261 Category: Unreleased Structures Category: Juo, Z.S [... |
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==Human BMP chimera BV261== | |||
<StructureSection load='6oml' size='340' side='right'caption='[[6oml]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6oml]] is a 2 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=6OML OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OML 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]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6oml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oml OCA], [https://pdbe.org/6oml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oml RCSB], [https://www.ebi.ac.uk/pdbsum/6oml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oml ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bone morphogenetic protein (BMP)/carriers approved for orthopedic procedures achieve efficacy superior or equivalent to autograft bone. However, required supraphysiological BMP concentrations have been associated with potential local and systemic adverse events. Suboptimal BMP/receptor binding and rapid BMP release from approved carriers may contribute to these outcomes. To address these issues and improve efficacy, we engineered chimeras with increased receptor binding by substituting BMP-6 and activin A receptor binding domains into BMP-2 and optimized a carrier for chimera retention and tissue ingrowth. BV-265, a BMP-2/BMP-6/activin A chimera, demonstrated increased binding affinity to BMP receptors, including activin-like kinase-2 (ALK2) critical for bone formation in people. BV-265 increased BMP intracellular signaling, osteogenic activity, and expression of bone-related genes in murine and human cells to a greater extent than BMP-2 and was not inhibited by BMP antagonist noggin or gremlin. BV-265 induced larger ectopic bone nodules in rats compared to BMP-2 and was superior to BMP-2, BMP-2/6, and other chimeras in nonhuman primate bone repair models. A composite matrix (CM) containing calcium-deficient hydroxyapatite granules suspended in a macroporous, fenestrated, polymer mesh-reinforced recombinant human type I collagen matrix demonstrated improved BV-265 retention, minimal inflammation, and enhanced handling. BV-265/CM was efficacious in nonhuman primate bone repair models at concentrations ranging from (1)/10 to (1)/30 of the BMP-2/absorbable collagen sponge (ACS) concentration approved for clinical use. Initial toxicology studies were negative. These results support evaluations of BV-265/CM as an alternative to BMP-2/ACS in clinical trials for orthopedic conditions requiring augmented healing. | |||
A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix.,Seeherman HJ, Berasi SP, Brown CT, Martinez RX, Juo ZS, Jelinsky S, Cain MJ, Grode J, Tumelty KE, Bohner M, Grinberg O, Orr N, Shoseyov O, Eyckmans J, Chen C, Morales PR, Wilson CG, Vanderploeg EJ, Wozney JM Sci Transl Med. 2019 Apr 24;11(489). pii: 11/489/eaar4953. doi:, 10.1126/scitranslmed.aar4953. PMID:31019025<ref>PMID:31019025</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Juo | <div class="pdbe-citations 6oml" style="background-color:#fffaf0;"></div> | ||
[[Category: Seeherman | |||
==See Also== | |||
*[[Bone morphogenetic protein 3D structures|Bone morphogenetic protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Juo ZS]] | |||
[[Category: Seeherman H]] | |||