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| <StructureSection load='6y9b' size='340' side='right'caption='[[6y9b]], [[Resolution|resolution]] 2.97Å' scene=''> | | <StructureSection load='6y9b' size='340' side='right'caption='[[6y9b]], [[Resolution|resolution]] 2.97Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6y9b]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y9B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y9B FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y9B FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=XP4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHATE'>XP4</scene></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]] 2.97Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STEAP1, PRSS24, STEAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=XP4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHATE'>XP4</scene></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6y9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y9b OCA], [http://pdbe.org/6y9b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y9b RCSB], [http://www.ebi.ac.uk/pdbsum/6y9b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y9b ProSAT]</span></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=6y9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y9b OCA], [https://pdbe.org/6y9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y9b RCSB], [https://www.ebi.ac.uk/pdbsum/6y9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y9b ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function ==
| |
| [[http://www.uniprot.org/uniprot/STEA1_HUMAN STEA1_HUMAN]] Metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+). Uses NAD(+) as acceptor.[UniProtKB:Q9CWR7]
| |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is an integral membrane protein that is highly upregulated on the cell surface of several human cancers, making it a promising therapeutic target to manage these diseases. It shares sequence homology with three enzymes (STEAP2-4) that catalyze the NADPH-dependent reduction of iron(III). However, STEAP1 lacks an intracellular NADPH-binding domain and does not exhibit cellular ferric-reductase activity. Thus, both the molecular function of STEAP1 and its role in cancer progression remain elusive. Here, we present a ~3.0 A cryo-EM structure of trimeric human STEAP1 bound to three antigen-binding fragments (Fabs) of the clinically used antibody mAb120.545. The structure disclosed that STEAP1 adopts a reductase-like conformation and interacts with the Fabs through its extracellular helices. Enzymatic assays in human cells revealed that STEAP1 promotes iron(III) reduction when fused to the intracellular NADPH-binding domain of its family member STEAP4, suggesting that STEAP1 functions as a ferric reductase in STEAP hetero-trimers. Our work provides a foundation for deciphering the molecular mechanisms of STEAP1 and may be instrumental in the design of new therapeutic strategies to target STEAP1 in cancer.
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| Cryo-EM structure and potential enzymatic function of human six-transmembrane epithelial antigen of the prostate 1.,Oosterheert W, Gros P J Biol Chem. 2020 May 14. pii: RA120.013690. doi: 10.1074/jbc.RA120.013690. PMID:32409586<ref>PMID:32409586</ref>
| | ==See Also== |
| | | *[[Antibody 3D structures|Antibody 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
| |
| <div class="pdbe-citations 6y9b" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Lk3 transgenic mice]]
| | [[Category: Gros P]] |
| [[Category: Gros, P]] | | [[Category: Oosterheert W]] |
| [[Category: Oosterheert, W]] | |
| [[Category: Integral membrane protein heme-binding protein oxidoreductase antibody-antigen complex]]
| |
| [[Category: Membrane protein]]
| |