8H1F
Aquifex aeolicus MutL endonuclease domain complexed with zinc ions after soaking
Summary for 8H1F
| Entry DOI | 10.2210/pdb8h1f/pdb |
| Descriptor | DNA mismatch repair protein MutL, ZINC ION, DI(HYDROXYETHYL)ETHER, ... (5 entities in total) |
| Functional Keywords | endonuclease, dna binding protein |
| Biological source | Aquifex aeolicus VF5 |
| Total number of polymer chains | 1 |
| Total formula weight | 12997.90 |
| Authors | |
| Primary citation | Fukui, K.,Yamamoto, T.,Murakawa, T.,Baba, S.,Kumasaka, T.,Yano, T. Catalytic mechanism of the zinc-dependent MutL endonuclease reaction. Life Sci Alliance, 6:-, 2023 Cited by PubMed Abstract: DNA mismatch repair endonuclease MutL binds two zinc ions. However, the endonuclease activity of MutL is drastically enhanced by other divalent metals such as manganese, implying that MutL binds another catalytic metal at some site other than the zinc-binding sites. Here, we solved the crystal structure of the endonuclease domain of MutL in the manganese- or cadmium-bound form, revealing that these metals compete with zinc at the same sites. Mass spectrometry revealed that the MutL yielded 5'-phosphate and 3'-OH products, which is characteristic of the two-metal-ion mechanism. Crystallographic analyses also showed that the position and flexibility of a highly conserved Arg of MutL altered depending on the presence of zinc/manganese or the specific inhibitor cadmium. Site-directed mutagenesis revealed that the Arg was critical for the catalysis. We propose that zinc ion and its binding sites are physiologically of catalytic importance and that the two-metal-ion mechanism works in the reaction, where the Arg plays a catalytic role. Our results also provide a mechanistic insight into the inhibitory effect of a mutagen/carcinogen, cadmium, on MutL. PubMed: 37487639DOI: 10.26508/lsa.202302001 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.22 Å) |
Structure validation
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