8h1g

The R406T mutant form of the Aquifex aeolicus MutL endonuclease domain

spinqualitylabelsall models 8h1g, resolution 1.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8h1g is a 1 chain structure with sequence from Aquifex aeolicus VF5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.43Å Ligands: CD, NA, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MUTL_AQUAE This protein is involved in the repair of mismatches in DNA. It is required for dam-dependent methyl-directed DNA mismatch repair. May act as a "molecular matchmaker", a protein that promotes the formation of a stable complex between two or more DNA-binding proteins in an ATP-dependent manner without itself being part of a final effector complex (By similarity). Publication Abstract from PubMed 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 Aquifex aeolicus 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 A. aeolicus 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. Catalytic mechanism of the zinc-dependent MutL endonuclease reaction.,Fukui K, Yamamoto T, Murakawa T, Baba S, Kumasaka T, Yano T Life Sci Alliance. 2023 Jul 24;6(10):e202302001. doi: 10.26508/lsa.202302001. , Print 2023 Oct. PMID:37487639 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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