21FM
Crystal structure of human dUTPase in complex with dUMP
This is a non-PDB format compatible entry.
Summary for 21FM
| Entry DOI | 10.2210/pdb21fm/pdb |
| Descriptor | Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (3 entities in total) |
| Functional Keywords | dutp, dump, dutpase, complex, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 53684.84 |
| Authors | |
| Primary citation | Nakashima, M.,Teruya, H.,Horinouchi, Y.,Murakawa, T.,Yano, T.,Fukui, K. Structural and Functional Roles of Arg85-Mediated Inter-Motif Interactions in Human dUTPase. Proteins, 2026 Cited by PubMed Abstract: Human dUTPase prevents uracil incorporation into DNA by hydrolyzing dUTP to dUMP, thereby maintaining genome integrity. Its catalytic activity is mediated by five conserved motifs (I-V) that cooperatively form the active site. Arg85, a highly conserved residue within Motif II, has been implicated in catalysis, but its contribution has not been defined at the structural level. Here, we examined the structural and functional roles of Arg85 using x-ray crystallography and enzymatic assays. Structures of wild-type and Arg85 mutant forms showed no major global changes. However, enzymatic analyses demonstrated that a positive charge at position 85 is required for efficient catalysis. Furthermore, comparisons among the wild-type and mutant structures revealed that Arg85 modulates the orientation of the conserved Arg128 through an inter-motif interaction network. Disruption of this network by mutations of Arg85 or Arg128 reduced the activity. These findings provide a mechanistic framework for disease-associated variants at Arg85 and Arg128. PubMed: 42532968DOI: 10.1002/prot.70164 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.31 Å) |
Structure validation
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