1M5X: Crystal structure of the homing endonuclease I-MsoI bound to its DNA substrate

Homing endonucleases are highly specific catalysts of DNA strand breaks that induce the transposition of mobile intervening sequences containing the endonuclease open reading frame. These enzymes recognize long DNA targets while tolerating individual sequence polymorphisms within those sites. Sequences of the homing endonucleases themselves diversify to a great extent after founding intron invasion events, generating highly divergent enzymes that recognize similar target sequences. Here, we visualize the mechanism of flexible DNA recognition and the pattern of structural divergence displayed by two homing endonuclease isoschizomers. We determined structures of I-CreI bound to two DNA target sites that differ at eight of 22 base-pairs, and the structure of an isoschizomer, I-MsoI, bound to a nearly identical DNA target site. This study illustrates several principles governing promiscuous base-pair recognition by DNA-binding proteins, and demonstrates that the isoschizomers display strikingly different protein/DNA contacts. The structures allow us to determine the information content at individual positions in the binding site as a function of the distribution of direct and water-mediated contacts to nucleotide bases, and provide an evolutionary snapshot of endonucleases at an early stage of divergence in their target specificity.
PDB ID: 1M5XDownload
MMDB ID: 50216
PDB Deposition Date: 2002/7/10
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Monomastix sp. OKE-1
Similar Structures:
Biological Unit for 1M5X: tetrameric; determined by author
Molecular Components in 1M5X
Label Count Molecule
Proteins (2 molecules)
DNA Endonuclease I-msoi
Molecule annotation
Nucleotides(2 molecules)
Molecule annotation
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB