7mhy
From Proteopedia
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| - | ==== | + | ==Human Hedgehog acyltransferase (HHAT) in complex with palmitoyl-CoA and two Fab antibody fragments== |
| - | <StructureSection load='7mhy' size='340' side='right'caption='[[7mhy]]' scene=''> | + | <StructureSection load='7mhy' size='340' side='right'caption='[[7mhy]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7mhy]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MHY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MHY FirstGlance]. <br> |
| - | </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=7mhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mhy OCA], [https://pdbe.org/7mhy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mhy RCSB], [https://www.ebi.ac.uk/pdbsum/7mhy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mhy ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[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=AJP:(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-2-[(2~{R},3~{R},4~{R},5~{R},6~{R})-2-(hydroxymethyl)-4,5-bis(oxidanyl)-6-[(1~{R},2~{S},3~{S},4~{R},5~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},15~{R},16~{R},18~{S})-5,7,9,13-tetramethyl-3,15-bis(oxidanyl)spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2-oxane]-16-yl]oxy-oxan-3-yl]oxy-5-oxidanyl-4-[(2~{S},3~{R},4~{S},5~{R})-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-oxan-3-yl]oxy-3,5-bis(oxidanyl)oxan-4-yl]oxy-oxane-3,4,5-triol'>AJP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PKZ:PALMITOYL-COA'>PKZ</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=7mhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mhy OCA], [https://pdbe.org/7mhy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mhy RCSB], [https://www.ebi.ac.uk/pdbsum/7mhy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mhy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [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. | ||
| + | == Function == | ||
| + | [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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo-electron microscopy structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer. | ||
| + | |||
| + | Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.,Jiang Y, Benz TL, Long SB Science. 2021 Jun 11;372(6547):1215-1219. doi: 10.1126/science.abg4998. PMID:34112694<ref>PMID:34112694</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7mhy" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Antibody 3D structures|Antibody 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Jiang Y]] | ||
| + | [[Category: Long SB]] | ||
Current revision
Human Hedgehog acyltransferase (HHAT) in complex with palmitoyl-CoA and two Fab antibody fragments
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