5MCP

Structure of IMP dehydrogenase from Ashbya gossypii bound to ATP

Summary for 5MCP

• Entry DOI: 10.2210/pdb5mcp/pdb
• Related: 4Z87 5TC3
• Descriptor: Inosine-5'-monophosphate dehydrogenase, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: imp dehydrogenase, ashbya gossypii, allosteric modulator, purine nucleotides, oxidoreductase
• Biological source: Ashbya gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056) (Yeast)
• Cellular location: Cytoplasm : Q756Z6
• Total number of polymer chains: 8
• Total formula weight: 465683.38

Authors

Winter, G.,Fernandez-Justel, D.,de Pereda, J.M.,Revuelta, J.L.,Buey, R.M. (deposition date: 2016-11-10, release date: 2017-06-14, Last modification date: 2024-01-17)

Primary citation

Buey, R.M.,Fernandez-Justel, D.,Marcos-Alcalde, I.,Winter, G.,Gomez-Puertas, P.,de Pereda, J.M.,Luis Revuelta, J.
A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases.
Sci Rep, 7:2648-2648, 2017

PubMed Abstract: 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.

PubMed: 28572600
DOI: 10.1038/s41598-017-02805-x

Experimental method

X-RAY DIFFRACTION (2.4 Å)