7q6z

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'''Unreleased structure'''
 
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The entry 7q6z is ON HOLD until Paper Publication
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==Structure of Hedgehog acyltransferase (HHAT) in complex with megabody 177 bound to IMP-1575==
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<StructureSection load='7q6z' size='340' side='right'caption='[[7q6z]], [[Resolution|resolution]] 3.59&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7q6z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q6Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q6Z FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.59&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9V3:2-(2-methylpropylamino)-1-[(4~{R})-4-(6-methylpyridin-2-yl)-6,7-dihydro-4~{H}-thieno[3,2-c]pyridin-5-yl]ethanone'>9V3</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7q6z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q6z OCA], [https://pdbe.org/7q6z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q6z RCSB], [https://www.ebi.ac.uk/pdbsum/7q6z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q6z ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/HHAT_HUMAN HHAT_HUMAN] Chondrodysplasia-difference of sex development syndrome. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/HHAT_HUMAN HHAT_HUMAN] Palmitoyl acyltransferase that catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling (PubMed:18534984, PubMed:24784881, PubMed:31875564). It also catalyzes N-terminal palmitoylation of DHH (PubMed:24784881). Promotes the transfer of palmitoyl-CoA from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane, where SHH palmitoylation occurs (PubMed:31875564). It is an essential factor for proper embryonic development and testicular organogenesis (PubMed:24784881).<ref>PMID:11486055</ref> <ref>PMID:18534984</ref> <ref>PMID:24784881</ref> <ref>PMID:31875564</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The Sonic Hedgehog (SHH) morphogen pathway is fundamental for embryonic development and stem cell maintenance and is implicated in various cancers. A key step in signaling is transfer of a palmitate group to the SHH N terminus, catalyzed by the multi-pass transmembrane enzyme Hedgehog acyltransferase (HHAT). We present the high-resolution cryo-EM structure of HHAT bound to substrate analog palmityl-coenzyme A and a SHH-mimetic megabody, revealing a heme group bound to HHAT that is essential for HHAT function. A structure of HHAT bound to potent small-molecule inhibitor IMP-1575 revealed conformational changes in the active site that occlude substrate binding. Our multidisciplinary analysis provides a detailed view of the mechanism by which HHAT adapts the membrane environment to transfer an acyl chain across the endoplasmic reticulum membrane. This structure of a membrane-bound O-acyltransferase (MBOAT) superfamily member provides a blueprint for other protein-substrate MBOATs and a template for future drug discovery.
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Authors: Coupland, C., Carrique, L., Siebold, C.
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Structure, mechanism, and inhibition of Hedgehog acyltransferase.,Coupland CE, Andrei SA, Ansell TB, Carrique L, Kumar P, Sefer L, Schwab RA, Byrne EFX, Pardon E, Steyaert J, Magee AI, Lanyon-Hogg T, Sansom MSP, Tate EW, Siebold C Mol Cell. 2021 Dec 16;81(24):5025-5038.e10. doi: 10.1016/j.molcel.2021.11.018. , Epub 2021 Dec 9. PMID:34890564<ref>PMID:34890564</ref>
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Description: Structure of Hedgehog acyltransferase (HHAT) in complex with megabody 177 bound to IMP-1575
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Coupland, C]]
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<div class="pdbe-citations 7q6z" style="background-color:#fffaf0;"></div>
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[[Category: Carrique, L]]
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== References ==
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[[Category: Siebold, C]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Escherichia coli K-12]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Carrique L]]
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[[Category: Coupland C]]
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[[Category: Siebold C]]

Current revision

Structure of Hedgehog acyltransferase (HHAT) in complex with megabody 177 bound to IMP-1575

PDB ID 7q6z

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