4MZL
Crystal Structure of MTIP from Plasmodium falciparum in complex with HBS myoA, a hydrogen bond surrogate myoA helix mimetic
Summary for 4MZL
| Entry DOI | 10.2210/pdb4mzl/pdb |
| Related | 4AOM 4MZJ 4MZK |
| Related PRD ID | PRD_001188 |
| Descriptor | Myosin A tail domain interacting protein, hydrogen bond surrogate (HBS) myoA helix mimetic (3 entities in total) |
| Functional Keywords | actomyosin motor, stapled peptides, protein binding-inhibitor complex, alpha-helix mimetic, protein binding/inhibitor |
| Biological source | Plasmodium falciparum 3D7 More |
| Cellular location | Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : 4MZL |
| Total number of polymer chains | 4 |
| Total formula weight | 37157.59 |
| Authors | Douse, C.H.,Garnett, J.A.,Maas, S.J.,Cota, E.,Tate, E.W. (deposition date: 2013-09-30, release date: 2013-11-06, Last modification date: 2024-10-16) |
| Primary citation | Douse, C.H.,Maas, S.J.,Thomas, J.C.,Garnett, J.A.,Sun, Y.,Cota, E.,Tate, E.W. Crystal Structures of Stapled and Hydrogen Bond Surrogate Peptides Targeting a Fully Buried Protein-Helix Interaction. Acs Chem.Biol., 8:506-512, 2014 Cited by PubMed Abstract: Constrained α-helical peptides are an exciting class of molecule designed to disrupt protein-protein interactions (PPIs) at a surface-exposed helix binding site. Complexes that engage more than one helical face account for over a third of structurally characterized helix PPIs, including several examples where the helix is fully buried. However, no constrained peptides have been reported that have targeted this class of interaction. We report the design of stapled and hydrogen bond surrogate (HBS) peptides mimicking the helical tail of the malaria parasite invasion motor myosin (myoA), which presents polar and hydrophobic functionality on all three faces in binding its partner, myoA tail interacting protein (MTIP), with high affinity. The first structures of these different constrained peptides bound to the same target are reported, enabling a direct comparison between these constraints and between staples based on monosubstituted pentenyl glycine (pGly) and disubstituted pentenyl alanine (pAla). Importantly, installation of these constraints does not disrupt native interactions in the buried site, so the affinity of the wild-type peptide is maintained. PubMed: 25084543DOI: 10.1021/cb500271c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.01 Å) |
Structure validation
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