View source for 6hcy


==human STEAP4 bound to NADP, FAD, heme and Fe(III)-NTA.==
<SX load='6hcy' size='340' side='right' viewer='molstar' caption='[[6hcy]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hcy]] is a 3 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=6HCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HCY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=44E:(2R)-3-(PHOSPHONOOXY)PROPANE-1,2-DIYL+DIHEXANOATE'>44E</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6hcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hcy OCA], [https://pdbe.org/6hcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hcy RCSB], [https://www.ebi.ac.uk/pdbsum/6hcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hcy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/STEA4_HUMAN STEA4_HUMAN] Metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+) (By similarity). Uses NADP(+) as acceptor (By similarity). Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses (By similarity). Associated with obesity and insulin-resistance (PubMed:18430367, PubMed:18381574). Involved in inflammatory arthritis, through the regulation of inflammatory cytokines (PubMed:19660107). Inhibits anchorage-independent cell proliferation (PubMed:19787193).<ref>PMID:18381574</ref> <ref>PMID:18430367</ref> <ref>PMID:19660107</ref> <ref>PMID:19787193</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Enzymes of the six-transmembrane epithelial antigen of the prostate (STEAP) family reduce Fe(3+) and Cu(2+) ions to facilitate metal-ion uptake by mammalian cells. STEAPs are highly upregulated in several types of cancer, making them potential therapeutic targets. However, the structural basis for STEAP-catalyzed electron transfer through an array of cofactors to metals at the membrane luminal side remains elusive. Here, we report cryo-electron microscopy structures of human STEAP4 in absence and presence of Fe(3+)-NTA. Domain-swapped, trimeric STEAP4 orients NADPH bound to a cytosolic domain onto axially aligned flavin-adenine dinucleotide (FAD) and a single b-type heme that cross the transmembrane-domain to enable electron transfer. Substrate binding within a positively charged ring indicates that iron gets reduced while in complex with its chelator. These molecular principles of iron reduction provide a basis for exploring STEAPs as therapeutic targets.

Cryo-EM structures of human STEAP4 reveal mechanism of iron(III) reduction.,Oosterheert W, van Bezouwen LS, Rodenburg RNP, Granneman J, Forster F, Mattevi A, Gros P Nat Commun. 2018 Oct 18;9(1):4337. doi: 10.1038/s41467-018-06817-7. PMID:30337524<ref>PMID:30337524</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6hcy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</SX>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Forster F]]
[[Category: Gros P]]
[[Category: Mattevi A]]
[[Category: Oosterheert W]]
[[Category: Rodenburg RNP]]
[[Category: Van Bezouwen LS]]