5mcp

Structure of IMP dehydrogenase from Ashbya gossypii bound to ATP

spinqualitylabelsall models 5mcp, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mcp is a 8 chain structure with sequence from Eremothecium gossypii ATCC 10895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: ATP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q756Z6_ASHGO Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.[HAMAP-Rule:MF_03156] Publication Abstract from PubMed Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for nucleotide metabolism and cell proliferation. Despite IMPDH is the target of drugs with antiviral, immunosuppressive and antitumor activities, its physiological mechanisms of regulation remain largely unknown. Using the enzyme from the industrial fungus Ashbya gossypii, we demonstrate that the binding of adenine and guanine nucleotides to the canonical nucleotide binding sites of the regulatory Bateman domain induces different enzyme conformations with significantly distinct catalytic activities. Thereby, the comparison of their high-resolution structures defines the mechanistic and structural details of a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity of eukaryotic IMPDHs. Remarkably, retinopathy-associated mutations lie within the mechanical hinges of the conformational change, highlighting its physiological relevance. Our results expand the mechanistic repertoire of Bateman domains and pave the road to new approaches targeting IMPDHs. A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases.,Buey RM, Fernandez-Justel D, Marcos-Alcalde I, Winter G, Gomez-Puertas P, de Pereda JM, Luis Revuelta J Sci Rep. 2017 Jun 1;7(1):2648. doi: 10.1038/s41598-017-02805-x. PMID:28572600 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Inosine monophosphate dehydrogenase 3D structures

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