5m05: Difference between revisions
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The | ==Chicken smooth muscle myosin motor domain co-crystallized with the specific CK-571 inhibitor, MgADP form== | ||
<StructureSection load='5m05' size='340' side='right'caption='[[5m05]], [[Resolution|resolution]] 2.67Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5m05]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5M05 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.675Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=52E:4-{[(2-CHLORO-3-FLUOROBENZYL)CARBAMOYL](METHYL)AMINO}-3,4-DIDEOXY-5-O-(ISOQUINOLIN-3-YLCARBAMOYL)-D-ERYTHRO-PENTITOL'>52E</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=5m05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m05 OCA], [https://pdbe.org/5m05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5m05 RCSB], [https://www.ebi.ac.uk/pdbsum/5m05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5m05 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MYH11_CHICK MYH11_CHICK] Muscle contraction. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Direct inhibition of smooth muscle myosin (SMM) is a potential means to treat hypercontractile smooth muscle diseases. The selective inhibitor CK-2018571 prevents strong binding to actin and promotes muscle relaxation in vitro and in vivo. The crystal structure of the SMM/drug complex reveals that CK-2018571 binds to a novel allosteric pocket that opens up during the "recovery stroke" transition necessary to reprime the motor. Trapped in an intermediate of this fast transition, SMM is inhibited with high selectivity compared with skeletal muscle myosin (IC50 = 9 nM and 11,300 nM, respectively), although all of the binding site residues are identical in these motors. This structure provides a starting point from which to design highly specific myosin modulators to treat several human diseases. It further illustrates the potential of targeting transition intermediates of molecular machines to develop exquisitely selective pharmacological agents. | |||
Highly selective inhibition of myosin motors provides the basis of potential therapeutic application.,Sirigu S, Hartman JJ, Planelles-Herrero VJ, Ropars V, Clancy S, Wang X, Chuang G, Qian X, Lu PP, Barrett E, Rudolph K, Royer C, Morgan BP, Stura EA, Malik FI, Houdusse AM Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7448-E7455. Epub 2016 Nov 4. PMID:27815532<ref>PMID:27815532</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5m05" style="background-color:#fffaf0;"></div> | ||
[[Category: Hartman | |||
[[Category: Houdusse | ==See Also== | ||
*[[Myosin 3D Structures|Myosin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Gallus gallus]] | |||
[[Category: Large Structures]] | |||
[[Category: Hartman J]] | |||
[[Category: Houdusse A]] | |||
[[Category: Sirigu S]] | |||
Latest revision as of 21:18, 1 November 2023
Chicken smooth muscle myosin motor domain co-crystallized with the specific CK-571 inhibitor, MgADP formChicken smooth muscle myosin motor domain co-crystallized with the specific CK-571 inhibitor, MgADP form
Structural highlights
FunctionMYH11_CHICK Muscle contraction. Publication Abstract from PubMedDirect inhibition of smooth muscle myosin (SMM) is a potential means to treat hypercontractile smooth muscle diseases. The selective inhibitor CK-2018571 prevents strong binding to actin and promotes muscle relaxation in vitro and in vivo. The crystal structure of the SMM/drug complex reveals that CK-2018571 binds to a novel allosteric pocket that opens up during the "recovery stroke" transition necessary to reprime the motor. Trapped in an intermediate of this fast transition, SMM is inhibited with high selectivity compared with skeletal muscle myosin (IC50 = 9 nM and 11,300 nM, respectively), although all of the binding site residues are identical in these motors. This structure provides a starting point from which to design highly specific myosin modulators to treat several human diseases. It further illustrates the potential of targeting transition intermediates of molecular machines to develop exquisitely selective pharmacological agents. Highly selective inhibition of myosin motors provides the basis of potential therapeutic application.,Sirigu S, Hartman JJ, Planelles-Herrero VJ, Ropars V, Clancy S, Wang X, Chuang G, Qian X, Lu PP, Barrett E, Rudolph K, Royer C, Morgan BP, Stura EA, Malik FI, Houdusse AM Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7448-E7455. Epub 2016 Nov 4. PMID:27815532[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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