3WZO: Crystal structure of the core streptavidin mutant V21 (Y22S/N23D/S27D/Y83S/R84K/E101D/R103K/E116N) complexed with biotin long tail (BTNtail) at 1.5 A resolution

Citation:
Abstract
For a multistep pre-targeting method using antibodies, a streptavidin mutant with low immunogenicity, termed low immunogenic streptavidin mutant No. 314 (LISA-314), was produced previously as a drug delivery tool. However, endogenous biotins (BTNs) with high affinity (Kd < 10(-10) M) for the binding pocket of LISA-314 prevents access of exogenous BTN-labelled anticancer drugs. In this study, we improve the binding pocket of LISA-314 to abolish its affinity for endogenous BTN species, therefore ensuring that the newly designed LISA-314 binds only artificial BTN analogue. The replacement of three amino acid residues was performed in two steps to develop a mutant termed V212, which selectively binds to 6-(5-((3aS,4S,6aR)-2-iminohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoic acid (iminobiotin long tail, IMNtail). Surface plasmon resonance results showed that V212 has a Kd value of 5.9 x 10(-7) M towards IMNtail, but no binding affinity for endogenous BTN species. This V212/IMNtail system will be useful as a novel delivery tool for anticancer therapy.
PDB ID: 3WZODownload
MMDB ID: 127041
PDB Deposition Date: 2014/10/1
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 3WZO: tetrameric; determined by author and by software (PISA)
Molecular Components in 3WZO
Label Count Molecule
Proteins (4 molecules)
4
Streptavidin
Molecule annotation
Chemicals (18 molecules)
1
4
2
3
3
9
4
2
* Click molecule labels to explore molecular sequence information.

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