3zyv

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the mouse liver Aldehyde Oxidase 3 (mAOX3)

Structural highlights

3zyv is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.545Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AOXC_MOUSE Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and phthalazine, as well as aldehydes, such as benzaldehyde, retinal and pyridoxal. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

BACKGROUND: Aldehyde oxidases have pharmacological relevance, and AOX3 is the major drug-metabolizing enzyme in rodents. RESULTS: The crystal structure of mouse AOX3 with kinetics and molecular docking studies provides insights into its enzymatic characteristics. CONCLUSION: Differences in substrate and inhibitor specificities can be rationalized by comparing the AOX3 and xanthine oxidase structures. SIGNIFICANCE: The first aldehyde oxidase structure represents a major advance for drug design and mechanistic studies. Aldehyde oxidases (AOXs) are homodimeric proteins belonging to the xanthine oxidase family of molybdenum-containing enzymes. Each 150-kDa monomer contains a FAD redox cofactor, two spectroscopically distinct [2Fe-2S] clusters, and a molybdenum cofactor located within the protein active site. AOXs are characterized by broad range substrate specificity, oxidizing different aldehydes and aromatic N-heterocycles. Despite increasing recognition of its role in the metabolism of drugs and xenobiotics, the physiological function of the protein is still largely unknown. We have crystallized and solved the crystal structure of mouse liver aldehyde oxidase 3 to 2.9 A. This is the first mammalian AOX whose structure has been solved. The structure provides important insights into the protein active center and further evidence on the catalytic differences characterizing AOX and xanthine oxidoreductase. The mouse liver aldehyde oxidase 3 three-dimensional structure combined with kinetic, mutagenesis data, molecular docking, and molecular dynamics studies make a decisive contribution to understand the molecular basis of its rather broad substrate specificity.

The first mammalian aldehyde oxidase crystal structure: insights into substrate specificity.,Coelho C, Mahro M, Trincao J, Carvalho AT, Ramos MJ, Terao M, Garattini E, Leimkuhler S, Romao MJ J Biol Chem. 2012 Nov 23;287(48):40690-702. doi: 10.1074/jbc.M112.390419. Epub, 2012 Sep 27. PMID:23019336^[5]

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

References

↑ Terao M, Kurosaki M, Marini M, Vanoni MA, Saltini G, Bonetto V, Bastone A, Federico C, Saccone S, Fanelli R, Salmona M, Garattini E. Purification of the aldehyde oxidase homolog 1 (AOH1) protein and cloning of the AOH1 and aldehyde oxidase homolog 2 (AOH2) genes. Identification of a novel molybdo-flavoprotein gene cluster on mouse chromosome 1. J Biol Chem. 2001 Dec 7;276(49):46347-63. PMID:11562361 doi:10.1074/jbc.M105744200
↑ Terao M, Kurosaki M, Barzago MM, Fratelli M, Bagnati R, Bastone A, Giudice C, Scanziani E, Mancuso A, Tiveron C, Garattini E. Role of the molybdoflavoenzyme aldehyde oxidase homolog 2 in the biosynthesis of retinoic acid: generation and characterization of a knockout mouse. Mol Cell Biol. 2009 Jan;29(2):357-77. PMID:18981221 doi:10.1128/MCB.01385-08
↑ Mahro M, Coelho C, Trincão J, Rodrigues D, Terao M, Garattini E, Saggu M, Lendzian F, Hildebrandt P, Romão MJ, Leimkühler S. Characterization and crystallization of mouse aldehyde oxidase 3: from mouse liver to Escherichia coli heterologous protein expression. Drug Metab Dispos. 2011 Oct;39(10):1939-45. PMID:21705476 doi:10.1124/dmd.111.040873
↑ Coelho C, Mahro M, Trincao J, Carvalho AT, Ramos MJ, Terao M, Garattini E, Leimkuhler S, Romao MJ. The first mammalian aldehyde oxidase crystal structure: insights into substrate specificity. J Biol Chem. 2012 Nov 23;287(48):40690-702. doi: 10.1074/jbc.M112.390419. Epub, 2012 Sep 27. PMID:23019336 doi:http://dx.doi.org/10.1074/jbc.M112.390419
↑ Coelho C, Mahro M, Trincao J, Carvalho AT, Ramos MJ, Terao M, Garattini E, Leimkuhler S, Romao MJ. The first mammalian aldehyde oxidase crystal structure: insights into substrate specificity. J Biol Chem. 2012 Nov 23;287(48):40690-702. doi: 10.1074/jbc.M112.390419. Epub, 2012 Sep 27. PMID:23019336 doi:http://dx.doi.org/10.1074/jbc.M112.390419

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/3zyv"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3zyv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZYV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.545&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aldehyde_oxidase Aldehyde oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.3.1 1.2.3.1] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MOS:DIOXOTHIOMOLYBDENUM(VI)+ION'>MOS</scene>, <scene name='pdbligand=MTE:PHOSPHONIC+ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER'>MTE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=3zyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zyv OCA], [https://pdbe.org/3zyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zyv RCSB], [https://www.ebi.ac.uk/pdbsum/3zyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zyv ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/AOXC_MOUSE AOXC_MOUSE] Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and phthalazine, as well as aldehydes, such as benzaldehyde, retinal and pyridoxal. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor.<ref>PMID:11562361</ref> <ref>PMID:18981221</ref> <ref>PMID:21705476</ref> <ref>PMID:23019336</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Aldehyde oxidase]]
 [[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Coelho, C]]
+[[Category: Coelho C]]
-[[Category: Garattini, E]]
+[[Category: Garattini E]]
-[[Category: Leimkuehler, S]]
+[[Category: Leimkuehler S]]
-[[Category: Mahro, M]]
+[[Category: Mahro M]]
-[[Category: Rodrigues, D]]
+[[Category: Rodrigues D]]
-[[Category: Romao, M J]]
+[[Category: Romao MJ]]
-[[Category: Terao, M]]
+[[Category: Terao M]]
-[[Category: Trincao, J]]
+[[Category: Trincao J]]
-[[Category: Molybdenum cofactor]]
-[[Category: Oxidoreductase]]

3zyv

From Proteopedia

Current revision

Crystal structure of the mouse liver Aldehyde Oxidase 3 (mAOX3)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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