4R1E
Crystal Structure of MTIP from Plasmodium falciparum in complex with a peptide-fragment chimera
Summary for 4R1E
| Entry DOI | 10.2210/pdb4r1e/pdb |
| Related | 4AOM 4MZJ 4MZK 4MZL |
| Descriptor | Myosin A tail domain interacting protein, Myosin-A, 5-{[(2-aminoethyl)sulfanyl]methyl}furan-2-carbaldehyde, ... (4 entities in total) |
| Functional Keywords | calmodulin-like, protein binding, myosin motor, fragment peptide, membrane, protein binding-inhibitor complex, protein binding/inhibitor |
| Biological source | Plasmodium falciparum More |
| Cellular location | Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : Q8IDR3 |
| Total number of polymer chains | 2 |
| Total formula weight | 18424.65 |
| Authors | Douse, C.H.,Vrielink, N.,Cota, E.,Tate, E.W. (deposition date: 2014-08-05, release date: 2014-11-12, Last modification date: 2023-09-20) |
| Primary citation | Douse, C.H.,Vrielink, N.,Wenlin, Z.,Cota, E.,Tate, E.W. Targeting a Dynamic Protein-Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex. Chemmedchem, 10:134-143, 2015 Cited by PubMed Abstract: Motility is a vital feature of the complex life cycle of Plasmodium falciparum, the apicomplexan parasite that causes human malaria. Processes such as host cell invasion are thought to be powered by a conserved actomyosin motor (containing myosin A or myoA), correct localization of which is dependent on a tight interaction with myosin A tail domain interacting protein (MTIP) at the inner membrane of the parasite. Although disruption of this protein-protein interaction represents an attractive means to investigate the putative roles of myoA-based motility and to inhibit the parasitic life cycle, no small molecules have been identified that bind to MTIP. Furthermore, it has not been possible to obtain a crystal structure of the free protein, which is highly dynamic and unstable in the absence of its natural myoA tail partner. Herein we report the de novo identification of the first molecules that bind to and stabilize MTIP via a fragment-based, integrated biophysical approach and structural investigations to examine the binding modes of hit compounds. The challenges of targeting such a dynamic system with traditional fragment screening workflows are addressed throughout. PubMed: 25367834DOI: 10.1002/cmdc.201402357 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
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