OCA at 07:43, 27 May 2020

OCA — Wed, 27 May 2020 07:43:38 GMT

←Older revision		Revision as of 07:43, 27 May 2020
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	==Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments==		==Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments==
-	<StructureSection load='6y9b' size='340' side='right'caption='[[6y9b]]' scene=''>	+	<StructureSection load='6y9b' size='340' side='right'caption='[[6y9b]], [[Resolution\|resolution]] 2.97Å' 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=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'>[[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>
-	</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>	+	</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='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='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>
	</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.
		+
		+	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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6y9b" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Gros P]]	+	[[Category: Lk3 transgenic mice]]
-	[[Category: Oosterheert W]]	+	[[Category: Gros, P]]
		+	[[Category: Oosterheert, W]]
		+	[[Category: Integral membrane protein heme-binding protein oxidoreductase antibody-antigen complex]]
		+	[[Category: Membrane protein]]

OCA at 05:52, 20 May 2020

OCA — Wed, 20 May 2020 05:52:32 GMT

←Older revision		Revision as of 05:52, 20 May 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6y9b is ON HOLD~~	+	==Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments==
-		+	<StructureSection load='6y9b' size='340' side='right'caption='[[6y9b]]' scene=''>
-	~~Authors: Oosterheert, W., Gros, P.~~	+	== Structural highlights ==
-		+	<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 [http://proteopedia.org/fgij/fg.htm?mol=6Y9B FirstGlance]. <br>
-	~~Description:~~ Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments	+	</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>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Oosterheert~~, W]]	+	__TOC__
-	[[Category: Gros, P]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Gros P]]
		+	[[Category: Oosterheert W]]

OCA: Protected "6y9b" [edit=sysop:move=sysop]

OCA — Wed, 18 Mar 2020 08:38:51 GMT

Protected "6y9b" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:38, 18 March 2020

OCA: New page: '''Unreleased structure''' The entry 6y9b is ON HOLD Authors: Oosterheert, W., Gros, P. Description: Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments [[Ca...

OCA — Wed, 18 Mar 2020 08:38:50 GMT

New page: '''Unreleased structure''' The entry 6y9b is ON HOLD Authors: Oosterheert, W., Gros, P. Description: Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments [[Ca...

New page

'''Unreleased structure'''

The entry 6y9b is ON HOLD

Authors: Oosterheert, W., Gros, P.

Description: Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments
[[Category: Unreleased Structures]]
[[Category: Oosterheert, W]]
[[Category: Gros, P]]

6y9b - Revision history

OCA at 07:43, 27 May 2020

OCA at 05:52, 20 May 2020

OCA: Protected "6y9b" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6y9b is ON HOLD Authors: Oosterheert, W., Gros, P. Description: Cryo-EM structure of trimeric human STEAP1 bound to three Fab120.545 fragments [[Ca...