6ijn

The D295N mutant of the N6-methyl-AMP deaminase from Arabidopsis thaliana complexed with N6m-AMP

spinqualitylabelsall models 6ijn, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ijn is a 1 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.66Å Ligands: 6MZ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ADAL_ARATH Catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotide N(6)-methyl-AMP (N6-mAMP) to produce inositol monophosphate (IMP) and methylamine (PubMed:29884623, PubMed:30721978, PubMed:31318636). Is required for the catabolism of cytosolic N6-mAMP, which is derived from the degradation of mRNA containing N6-methylated adenine (m6A) (PubMed:29884623). Does not possess deaminase activity toward adenosine, AMP, N6-methyladenosine, or N6-mATP in vitro (PubMed:29884623). Publication Abstract from PubMed Adenosine deaminase is involved in adenosine degradation and salvage pathway, and plays important physiological roles in purine metabolism. Recently, a novel type of adenosine deaminase-like protein has been identified, which displays deamination activity toward N6-methyl-adenosine monophosphate but not adenosine or AMP, and was consequently named N6-methyl-AMP deaminase (MAPDA). The underlying structural basis of MAPDA recognition and catalysis is poorly understood. Here, we present the crystal structures of MAPDA from Arabidopsis thaliana in the free and in the ligand-bound forms. The protein contains a conserved (beta/alpha)8 Tim-barrel domain and a typical zinc-binding site, but it also exhibits idiosyncratic local differences for two flexible helices important for substrate binding. The extensive interactions between the N6-methyl-AMP substrate or the inosine monophosphate product and the enzyme were identified, and subsequently evaluated by the deamination activity assays. Importantly, each structure reported here represents a different stage of the catalytic pathway and their structural differences suggested that the enzyme can exist in two distinct conformational states. The open state switches to the closed one upon the binding of ligands, brought about by the two critical helices. Our structural studies provide the first look of this important metabolic enzyme and shed lights on its catalytic pathway, which holds promise for the structure-based drug design for MAPDA-related diseases. Alternative conformation induced by substrate binding for Arabidopsis thaliana N6-methyl-AMP deaminase.,Jia Q, Xie W Nucleic Acids Res. 2019 Feb 5. pii: 5306579. doi: 10.1093/nar/gkz070. PMID:30721978 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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