6T1B

Crystal structure of YlmD from Geobacillus stearothermophilus in complex with inosine

Summary for 6T1B

• Entry DOI: 10.2210/pdb6t1b/pdb
• Related: 6T0Y
• Descriptor: YlmD, INOSINE, ZINC ION, ... (4 entities in total)
• Functional Keywords: purine metabolism, enzyme, deaminase, phosphorylase, nucleoside salvage, zinc-binding protein, hydrolase
• Biological source: Geobacillus stearothermophilus
• Total number of polymer chains: 1
• Total formula weight: 30333.96

Authors

Reikine, S.,Modis, Y. (deposition date: 2019-10-03, release date: 2020-01-29, Last modification date: 2024-01-24)

Primary citation

Cader, M.Z.,de Almeida Rodrigues, R.P.,West, J.A.,Sewell, G.W.,Md-Ibrahim, M.N.,Reikine, S.,Sirago, G.,Unger, L.W.,Iglesias-Romero, A.B.,Ramshorn, K.,Haag, L.M.,Saveljeva, S.,Ebel, J.F.,Rosenstiel, P.,Kaneider, N.C.,Lee, J.C.,Lawley, T.D.,Bradley, A.,Dougan, G.,Modis, Y.,Griffin, J.L.,Kaser, A.
FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.
Cell, 180:278-, 2020

PubMed Abstract: Mutations in FAMIN cause arthritis and inflammatory bowel disease in early childhood, and a common genetic variant increases the risk for Crohn's disease and leprosy. We developed an unbiased liquid chromatography-mass spectrometry screen for enzymatic activity of this orphan protein. We report that FAMIN phosphorolytically cleaves adenosine into adenine and ribose-1-phosphate. Such activity was considered absent from eukaryotic metabolism. FAMIN and its prokaryotic orthologs additionally have adenosine deaminase, purine nucleoside phosphorylase, and S-methyl-5'-thioadenosine phosphorylase activity, hence, combine activities of the namesake enzymes of central purine metabolism. FAMIN enables in macrophages a purine nucleotide cycle (PNC) between adenosine and inosine monophosphate and adenylosuccinate, which consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity. This macrophage PNC synchronizes mitochondrial activity with glycolysis by balancing electron transfer to mitochondria, thereby supporting glycolytic activity and promoting oxidative phosphorylation and mitochondrial H and phosphate recycling.

PubMed: 31978345
DOI: 10.1016/j.cell.2019.12.017

Experimental method

X-RAY DIFFRACTION (1.2 Å)