3V1E: Crystal structure of de novo designed MID1-zinc H12E mutant

Computationally designing protein-protein interactions with high affinity and desired orientation is a challenging task. Incorporating metal-binding sites at the target interface may be one approach for increasing affinity and specifying the binding mode, thereby improving robustness of designed interactions for use as tools in basic research as well as in applications from biotechnology to medicine. Here we describe a Rosetta-based approach for the rational design of a protein monomer to form a zinc-mediated, symmetric homodimer. Our metal interface design, named MID1 (NESG target ID OR37), forms a tight dimer in the presence of zinc (MID1-zinc) with a dissociation constant <30 nM. Without zinc the dissociation constant is 4 muM. The crystal structure of MID1-zinc shows good overall agreement with the computational model, but only three out of four designed histidines coordinate zinc. However, a histidine-to-glutamate point mutation resulted in four-coordination of zinc, and the resulting metal binding site and dimer orientation closely matches the computational model (Calpha rmsd = 1.4 A).
PDB ID: 3V1EDownload
MMDB ID: 96400
PDB Deposition Date: 2011/12/9
Updated in MMDB: 2018/07
Experimental Method:
x-ray diffraction
Resolution: 1.073  Å
Source Organism:
Similar Structures:
Biological Unit for 3V1E: dimeric; determined by author and by software (PISA)
Molecular Components in 3V1E
Label Count Molecule
Proteins (2 molecules)
Computational Design, Mid1-zinc H12e Mutant
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB