7mi1: Difference between revisions
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<StructureSection load='7mi1' size='340' side='right'caption='[[7mi1]], [[Resolution|resolution]] 4.50Å' scene=''> | <StructureSection load='7mi1' size='340' side='right'caption='[[7mi1]], [[Resolution|resolution]] 4.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7mi1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7mi1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MI1 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.5Å</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=7mi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mi1 OCA], [https://pdbe.org/7mi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mi1 RCSB], [https://www.ebi.ac.uk/pdbsum/7mi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mi1 ProSAT]</span></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=7mi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mi1 OCA], [https://pdbe.org/7mi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mi1 RCSB], [https://www.ebi.ac.uk/pdbsum/7mi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mi1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/DYHC_YEAST DYHC_YEAST | [https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/DYHC_YEAST DYHC_YEAST] Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required to maintain uniform nuclear distribution in hyphae. May play an important role in the proper orientation of the mitotic spindle into the budding daughter cell yeast. Probably required for normal progression of the cell cycle.<ref>PMID:15642746</ref> | ||
<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: | [[Category: Escherichia virus T4]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: | [[Category: Bhabha G]] | ||
[[Category: | [[Category: Ekiert DC]] | ||
[[Category: | [[Category: Kapoor TM]] | ||
[[Category: | [[Category: Santarossa CC]] | ||
Latest revision as of 19:12, 18 October 2023
X-ray structure of yeast dynein motor domain in the presence of a pyrazolo-pyrimidinone-based compound (compound 20)X-ray structure of yeast dynein motor domain in the presence of a pyrazolo-pyrimidinone-based compound (compound 20)
Structural highlights
FunctionD9IEF7_BPT4 DYHC_YEAST Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required to maintain uniform nuclear distribution in hyphae. May play an important role in the proper orientation of the mitotic spindle into the budding daughter cell yeast. Probably required for normal progression of the cell cycle.[1] Publication Abstract from PubMedCytoplasmic dyneins are AAA (ATPase associated with diverse cellular activities) motor proteins responsible for microtubule minus-end-directed intracellular transport. Dynein's unusually large size, four distinct nucleotide-binding sites, and conformational dynamics pose challenges for the design of potent and selective chemical inhibitors. Here we use structural approaches to develop a model for the inhibition of a well-characterized S. cerevisiae dynein construct by pyrazolo-pyrimidinone-based compounds. These data, along with functional assays of dynein motility and mutagenesis studies, suggest that the compounds inhibit dynein by engaging the regulatory ATPase sites in the AAA3 and AAA4 domains, and not by interacting with dynein's main catalytic site in the AAA1 domain. A double Walker B mutation of the AAA3 and AAA4 sites substantially reduces enzyme activity, suggesting that targeting these regulatory domains is sufficient to inhibit dynein. Our findings reveal how chemical inhibitors can be designed to disrupt allosteric communication across dynein's AAA domains. Targeting allostery in the Dynein motor domain with small molecule inhibitors.,Santarossa CC, Mickolajczyk KJ, Steinman JB, Urnavicius L, Chen N, Hirata Y, Fukase Y, Coudray N, Ekiert DC, Bhabha G, Kapoor TM Cell Chem Biol. 2021 May 17. pii: S2451-9456(21)00217-8. doi:, 10.1016/j.chembiol.2021.04.024. PMID:34015309[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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