4r1e

Crystal Structure of MTIP from Plasmodium falciparum in complex with a peptide-fragment chimera

spinqualitylabelsall models 4r1e, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4r1e is a 2 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.98Å Ligands: 3EC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8I4W8_PLAF7 Publication Abstract from PubMed 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. Targeting a Dynamic Protein-Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex.,Douse CH, Vrielink N, Wenlin Z, Cota E, Tate EW ChemMedChem. 2014 Nov 3. doi: 10.1002/cmdc.201402357. PMID:25367834 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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