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6hcy

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Revision as of 07:52, 6 November 2019

human STEAP4 bound to NADP, FAD, heme and Fe(III)-NTA.

Structural highlights

6hcy is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Gene:	STEAP4, STAMP2, TNFAIP9 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Arner P, Stenson BM, Dungner E, Naslund E, Hoffstedt J, Ryden M, Dahlman I. Expression of six transmembrane protein of prostate 2 in human adipose tissue associates with adiposity and insulin resistance. J Clin Endocrinol Metab. 2008 Jun;93(6):2249-54. doi: 10.1210/jc.2008-0206. Epub , 2008 Apr 1. PMID:18381574 doi:http://dx.doi.org/10.1210/jc.2008-0206
↑ Zhang CM, Chi X, Wang B, Zhang M, Ni YH, Chen RH, Li XN, Guo XR. Downregulation of STEAP4, a highly-expressed TNF-alpha-inducible gene in adipose tissue, is associated with obesity in humans. Acta Pharmacol Sin. 2008 May;29(5):587-92. doi: 10.1111/j.1745-7254.2008.00793.x. PMID:18430367 doi:http://dx.doi.org/10.1111/j.1745-7254.2008.00793.x
↑ Inoue A, Matsumoto I, Tanaka Y, Iwanami K, Kanamori A, Ochiai N, Goto D, Ito S, Sumida T. Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis. Arthritis Res Ther. 2009;11(4):R118. doi: 10.1186/ar2779. Epub 2009 Aug 6. PMID:19660107 doi:http://dx.doi.org/10.1186/ar2779
↑ Tamura T, Chiba J. STEAP4 regulates focal adhesion kinase activation and CpG motifs within STEAP4 promoter region are frequently methylated in DU145, human androgen-independent prostate cancer cells. Int J Mol Med. 2009 Nov;24(5):599-604. PMID:19787193
↑ Oosterheert W, van Bezouwen LS, Rodenburg RNP, Granneman J, Forster F, Mattevi A, Gros P. Cryo-EM structures of human STEAP4 reveal mechanism of iron(III) reduction. Nat Commun. 2018 Oct 18;9(1):4337. doi: 10.1038/s41467-018-06817-7. PMID:30337524 doi:http://dx.doi.org/10.1038/s41467-018-06817-7

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6hcy"

@@ Line 1: / Line 1: @@
 ==human STEAP4 bound to NADP, FAD, heme and Fe(III)-NTA.==
-<StructureSection load='6hcy' size='340' side='right' caption='[[6hcy]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+<StructureSection load='6hcy' size='340' side='right'caption='[[6hcy]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6hcy]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HCY FirstGlance]. <br>
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bezouwen, L S.van]]
 [[Category: Forster, F]]

6hcy

From Proteopedia

Revision as of 07:52, 6 November 2019

human STEAP4 bound to NADP, FAD, heme and Fe(III)-NTA.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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