5i91

Structure of Mouse Acirecutone dioxygenase with to Ni2+ and 2-keto-4-(methylthio)-butyric acid in the active site

spinqualitylabelsall models 5i91, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5i91 is a 1 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 1.76Å Ligands: KMT, NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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