4n3m: Difference between revisions
No edit summary |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Joint neutron/X-ray structure of urate oxidase in complex with 8-azaxanthine== | ||
[[http://www.uniprot.org/uniprot/URIC_ASPFL URIC_ASPFL | <StructureSection load='4n3m' size='340' side='right'caption='[[4n3m]], [[Resolution|resolution]] 1.92Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4n3m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_flavus Aspergillus flavus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N3M FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Hybrid , Neutron Diffraction , X-ray diffraction, [[Resolution|Resolution]] 1.919Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AZA:8-AZAXANTHINE'>AZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</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=4n3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n3m OCA], [https://pdbe.org/4n3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n3m RCSB], [https://www.ebi.ac.uk/pdbsum/4n3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n3m ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/URIC_ASPFL URIC_ASPFL] Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Urate oxidase transforms uric acid to 5-hydroxyisourate without the help of cofactors, but the catalytic mechanism has remained enigmatic, as the protonation state of the substrate could not be reliably deduced. We have determined the neutron structure of urate oxidase, providing unique information on the proton positions. A neutron crystal structure inhibited by a chloride anion at 2.3 A resolution shows that the substrate is in fact 8-hydroxyxanthine, the enol tautomer of urate. We have also determined the neutron structure of the complex with the inhibitor 8-azaxanthine at 1.9 A resolution, showing the protonation states of the K10-T57-H256 catalytic triad. Together with X-ray data and quantum chemical calculations, these structures allow us to identify the site of the initial substrate protonation and elucidate why the enzyme is inhibited by a chloride anion. | |||
The neutron structure of urate oxidase resolves a long-standing mechanistic conundrum and reveals unexpected changes in protonation.,Oksanen E, Blakeley MP, El-Hajji M, Ryde U, Budayova-Spano M PLoS One. 2014 Jan 23;9(1):e86651. doi: 10.1371/journal.pone.0086651. eCollection, 2014 Jan 23. PMID:24466188<ref>PMID:24466188</ref> | |||
[[ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: | <div class="pdbe-citations 4n3m" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Urate oxidase 3D structures|Urate oxidase 3D structures]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus flavus]] | |||
[[Category: Large Structures]] | |||
[[Category: Blakeley MP]] | |||
[[Category: Budayova-Spano M]] | |||
[[Category: Oksanen E]] | |||
Latest revision as of 10:13, 27 November 2024
Joint neutron/X-ray structure of urate oxidase in complex with 8-azaxanthineJoint neutron/X-ray structure of urate oxidase in complex with 8-azaxanthine
Structural highlights
FunctionURIC_ASPFL Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin. Publication Abstract from PubMedUrate oxidase transforms uric acid to 5-hydroxyisourate without the help of cofactors, but the catalytic mechanism has remained enigmatic, as the protonation state of the substrate could not be reliably deduced. We have determined the neutron structure of urate oxidase, providing unique information on the proton positions. A neutron crystal structure inhibited by a chloride anion at 2.3 A resolution shows that the substrate is in fact 8-hydroxyxanthine, the enol tautomer of urate. We have also determined the neutron structure of the complex with the inhibitor 8-azaxanthine at 1.9 A resolution, showing the protonation states of the K10-T57-H256 catalytic triad. Together with X-ray data and quantum chemical calculations, these structures allow us to identify the site of the initial substrate protonation and elucidate why the enzyme is inhibited by a chloride anion. The neutron structure of urate oxidase resolves a long-standing mechanistic conundrum and reveals unexpected changes in protonation.,Oksanen E, Blakeley MP, El-Hajji M, Ryde U, Budayova-Spano M PLoS One. 2014 Jan 23;9(1):e86651. doi: 10.1371/journal.pone.0086651. eCollection, 2014 Jan 23. PMID:24466188[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||