View source for 5i91


==Structure of Mouse Acirecutone dioxygenase with to Ni2+ and 2-keto-4-(methylthio)-butyric acid in the active site==
<StructureSection load='5i91' size='340' side='right'caption='[[5i91]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5i91]] is a 1 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=5I91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I91 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KMT:4-(METHYLSULFANYL)-2-OXOBUTANOIC+ACID'>KMT</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=5i91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i91 OCA], [https://pdbe.org/5i91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i91 RCSB], [https://www.ebi.ac.uk/pdbsum/5i91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i91 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MTND_MOUSE MTND_MOUSE] Catalyzes the formation of formate and 2-keto-4-methylthiobutyrate (KMTB) from 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene). Also down-regulates cell migration mediated by MMP14 (By similarity).[HAMAP-Rule:MF_03154]
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== Publication Abstract from PubMed ==
The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella oxytoca are the only known pair of naturally occurring metalloenzymes with distinct chemical and physical properties determined solely by the identity of the divalent transition metal ion (Fe(2+) or Ni(2+)) in the active site. We now show that this dual chemistry can also occur in mammals. ARD from Mus musculus (MmARD) was studied to relate the metal ion identity and three-dimensional structure to enzyme function. The iron-containing isozyme catalyzes the cleavage of 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, which is the penultimate step in methionine salvage. The nickel-bound form of ARD catalyzes an off-pathway reaction resulting in formate, carbon monoxide (CO), and 3-(thiomethyl) propionate. Recombinant MmARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. The Fe(2+)-bound protein, which shows about 10-fold higher activity than that of others, catalyzes on-pathway chemistry, whereas the Ni(2+), Co(2+), or Mn(2+) forms exhibit off-pathway chemistry, as has been seen with ARD from Klebsiella. Thermal stability of the isozymes is strongly affected by the metal ion identity, with Ni(2+)-bound MmARD being the most stable, followed by Co(2+) and Fe(2+), and Mn(2+)-bound ARD being the least stable. Ni(2+)- and Co(2+)-bound MmARD were crystallized, and the structures of the two proteins found to be similar. Enzyme-ligand complexes provide insight into substrate binding, metal coordination, and the catalytic mechanism.

Metal-Dependent Function of a Mammalian Acireductone Dioxygenase.,Deshpande AR, Wagenpfeil K, Pochapsky TC, Petsko GA, Ringe D Biochemistry. 2016 Mar 8;55(9):1398-407. doi: 10.1021/acs.biochem.5b01319. Epub, 2016 Feb 24. PMID:26858196<ref>PMID:26858196</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5i91" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Deshpande AR]]
[[Category: Petsko GA]]
[[Category: Pochapsky TC]]
[[Category: Ringe D]]
[[Category: Robinson H]]
[[Category: Wagenpfeil K]]