8u7y

From Proteopedia

(Difference between revisions)

Current revision

Structural Basis of Human NOX5 Activation

Structural highlights

8u7y is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.06Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NOX5_HUMAN Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin.^[1] ^[2] ^[3]

Publication Abstract from PubMed

NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.

Structural basis of human NOX5 activation.,Cui C, Jiang M, Jain N, Das S, Lo YH, Kermani AA, Pipatpolkai T, Sun J Nat Commun. 2024 May 11;15(1):3994. doi: 10.1038/s41467-024-48467-y. PMID:38734761^[4]

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

References

↑ Banfi B, Molnar G, Maturana A, Steger K, Hegedus B, Demaurex N, Krause KH. A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem. 2001 Oct 5;276(40):37594-601. doi: 10.1074/jbc.M103034200. Epub 2001, Aug 1. PMID:11483596 doi:http://dx.doi.org/10.1074/jbc.M103034200
↑ Brar SS, Corbin Z, Kennedy TP, Hemendinger R, Thornton L, Bommarius B, Arnold RS, Whorton AR, Sturrock AB, Huecksteadt TP, Quinn MT, Krenitsky K, Ardie KG, Lambeth JD, Hoidal JR. NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol. 2003 Aug;285(2):C353-69. doi:, 10.1152/ajpcell.00525.2002. Epub 2003 Apr 9. PMID:12686516 doi:http://dx.doi.org/10.1152/ajpcell.00525.2002
↑ BelAiba RS, Djordjevic T, Petry A, Diemer K, Bonello S, Banfi B, Hess J, Pogrebniak A, Bickel C, Gorlach A. NOX5 variants are functionally active in endothelial cells. Free Radic Biol Med. 2007 Feb 15;42(4):446-59. Epub 2006 Nov 3. PMID:17275676 doi:http://dx.doi.org/S0891-5849(06)00701-5
↑ Cui C, Jiang M, Jain N, Das S, Lo YH, Kermani AA, Pipatpolkai T, Sun J. Structural basis of human NOX5 activation. Nat Commun. 2024 May 11;15(1):3994. PMID:38734761 doi:10.1038/s41467-024-48467-y

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/8u7y"

Categories: Homo sapiens | Large Structures | Cui C | Jiang M | Sun J

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8u7y is ON HOLD  until Paper Publication
+==Structural Basis of Human NOX5 Activation==
+<StructureSection load='8u7y' size='340' side='right'caption='[[8u7y]], [[Resolution|resolution]] 4.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8u7y]] is a 2 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=8U7Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8U7Y 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]] 4.06&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8u7y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8u7y OCA], [https://pdbe.org/8u7y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8u7y RCSB], [https://www.ebi.ac.uk/pdbsum/8u7y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8u7y ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NOX5_HUMAN NOX5_HUMAN] Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin.<ref>PMID:11483596</ref> <ref>PMID:12686516</ref> <ref>PMID:17275676</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.
-Authors:
+Structural basis of human NOX5 activation.,Cui C, Jiang M, Jain N, Das S, Lo YH, Kermani AA, Pipatpolkai T, Sun J Nat Commun. 2024 May 11;15(1):3994. doi: 10.1038/s41467-024-48467-y. PMID:38734761<ref>PMID:38734761</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8u7y" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Cui C]]
+[[Category: Jiang M]]
+[[Category: Sun J]]

8u7y

From Proteopedia

Current revision

Structural Basis of Human NOX5 Activation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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