6btp: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6btp is ON HOLD
+==BMP1 complexed with a hydroxamate==
+<StructureSection load='6btp' size='340' side='right'caption='[[6btp]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6btp]] 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=6BTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BTP 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]] 1.93&#8491;</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=E8J:(1~{R},3~{S},4~{S})-~{N}-(3-methoxypyrazin-2-yl)-2-[(2~{R})-2-[2-(oxidanylamino)-2-oxidanylidene-ethyl]heptanoyl]-2-azabicyclo[2.2.1]heptane-3-carboxamide'>E8J</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6btp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6btp OCA], [https://pdbe.org/6btp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6btp RCSB], [https://www.ebi.ac.uk/pdbsum/6btp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6btp ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/BMP1_HUMAN BMP1_HUMAN] Defects in BMP1 are the cause of osteogenesis imperfecta 13 (OI13) [MIM:[https://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 ==
+[https://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 hydroxamate
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Gampe, R]]
+<div class="pdbe-citations 6btp" style="background-color:#fffaf0;"></div>
-[[Category: Shewchuk, L]]
+==See Also==
+*[[Bone morphogenetic protein 3D structures|Bone morphogenetic protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Gampe R]]
+[[Category: Shewchuk L]]