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| | ==Crystal Structure of MTIP from Plasmodium falciparum in complex with a peptide-fragment chimera== | | ==Crystal Structure of MTIP from Plasmodium falciparum in complex with a peptide-fragment chimera== |
| - | <StructureSection load='4r1e' size='340' side='right' caption='[[4r1e]], [[Resolution|resolution]] 1.98Å' scene=''> | + | <StructureSection load='4r1e' size='340' side='right'caption='[[4r1e]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r1e]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R1E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r1e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R1E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3EC:5-{[(2-AMINOETHYL)SULFANYL]METHYL}FURAN-2-CARBALDEHYDE'>3EC</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3EC:5-{[(2-AMINOETHYL)SULFANYL]METHYL}FURAN-2-CARBALDEHYDE'>3EC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4aom|4aom]], [[4mzj|4mzj]], [[4mzk|4mzk]], [[4mzl|4mzl]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1e OCA], [https://pdbe.org/4r1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r1e RCSB], [https://www.ebi.ac.uk/pdbsum/4r1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r1e ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTIP, PFL2225w ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r1e OCA], [http://pdbe.org/4r1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r1e RCSB], [http://www.ebi.ac.uk/pdbsum/4r1e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r1e ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MYOA_PLAF7 MYOA_PLAF7]] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity). | + | [https://www.uniprot.org/uniprot/Q8I4W8_PLAF7 Q8I4W8_PLAF7] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Plaf7]] | + | [[Category: Large Structures]] |
| - | [[Category: Cota, E]] | + | [[Category: Plasmodium falciparum 3D7]] |
| - | [[Category: Douse, C H]] | + | [[Category: Cota E]] |
| - | [[Category: Tate, E W]]
| + | [[Category: Douse CH]] |
| - | [[Category: Vrielink, N]] | + | [[Category: Tate EW]] |
| - | [[Category: Calmodulin-like]] | + | [[Category: Vrielink N]] |
| - | [[Category: Fragment peptide]] | + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Myosin motor]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein binding-inhibitor complex]]
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| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Douse CH, Vrielink N, Wenlin Z, Cota E, Tate EW. Targeting a Dynamic Protein-Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex. ChemMedChem. 2014 Nov 3. doi: 10.1002/cmdc.201402357. PMID:25367834 doi:http://dx.doi.org/10.1002/cmdc.201402357
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