6SCX
Crystal structure of the catalytic domain of human NUDT12 in complex with 7-methyl-guanosine-5'-triphosphate
Summary for 6SCX
| Entry DOI | 10.2210/pdb6scx/pdb |
| Descriptor | Peroxisomal NADH pyrophosphatase NUDT12, CADMIUM ION, 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | nudix protein, denadding enzyme, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 122628.90 |
| Authors | McCarthy, A.A.,Chen, K.M.,Wu, H.,Li, L.,Homolka, D.,Gos, P.,Fleury-Olela, F.,Pillai, R.S. (deposition date: 2019-07-25, release date: 2020-01-08, Last modification date: 2024-11-06) |
| Primary citation | Wu, H.,Li, L.,Chen, K.M.,Homolka, D.,Gos, P.,Fleury-Olela, F.,McCarthy, A.A.,Pillai, R.S. Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs. Cell Rep, 29:4422-4434.e13, 2019 Cited by PubMed Abstract: RNA polymerase II transcripts receive a protective 5',5'-triphosphate-linked 7-methylguanosine (mG) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs. PubMed: 31875550DOI: 10.1016/j.celrep.2019.11.108 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.92 Å) |
Structure validation
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