spacer
spacer

PDBsum entry 1yv3

Go to PDB code: 
protein ligands metals links
Contractile protein PDB id
1yv3
Jmol
Contents
Protein chain
703 a.a. *
Ligands
VO4
ADP
BIT
EDO
Metals
_MG ×2
Waters ×678
* Residue conservation analysis
PDB id:
1yv3
Name: Contractile protein
Title: The structural basis of blebbistatin inhibition and specificity for myosin ii
Structure: Myosin ii heavy chain. Chain: a
Source: Dictyostelium discoideum. Organism_taxid: 44689
Resolution:
2.00Å     R-factor:   0.175     R-free:   0.215
Authors: J.S.Allingham,R.Smith,I.Rayment
Key ref:
J.S.Allingham et al. (2005). The structural basis of blebbistatin inhibition and specificity for myosin II. Nat Struct Mol Biol, 12, 378-379. PubMed id: 15750603 DOI: 10.1038/nsmb908
Date:
14-Feb-05     Release date:   08-Mar-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08799  (MYS2_DICDI) -  Myosin-2 heavy chain
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2116 a.a.
703 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     myosin complex   1 term 
  Biochemical function     ATP binding     2 terms  

 

 
DOI no: 10.1038/nsmb908 Nat Struct Mol Biol 12:378-379 (2005)
PubMed id: 15750603  
 
 
The structural basis of blebbistatin inhibition and specificity for myosin II.
J.S.Allingham, R.Smith, I.Rayment.
 
  ABSTRACT  
 
Molecular motors play a central role in cytoskeletal-mediated cellular processes and thus present an excellent target for cellular control by pharmacological agents. Yet very few such compounds have been found. We report here the structure of blebbistatin, which inhibits specific myosin isoforms, bound to the motor domain of Dictyostelium discoideum myosin II. This reveals the structural basis for its specificity and provides insight into the development of new agents.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Blebbistatin chemical structure and binding site on MgADP -vanadate myosin II. (a) Chemical structure of (S)-blebbistatin ( -)-1-phenyl-1,2,3,4-tetrahydro-4-hydroxypyrrolo[2,3-b]-7-methylquinolin-4-one. (b) Blebbistatin -myosin complex. Blebbistatin and MgADP -vanadate are in space-filling and ball-and-stick representations, respectively. The coordinates and X-ray data for the D. discoideum myosin S1dC -blebbistatin complex have been deposited in the Protein Data Bank (accession code 1YV3).
Figure 2.
Figure 2. Blebbistatin-binding site and contact residue conservation for different myosin isoforms. (a) Blebbistatin binds within the apex of the myosin cleft at the opposite end of the 'phosphate tube' from MgADP -vanadate. The F[o] - F[c] electron density omit map for blebbistatin was contoured at 3 . (b) Selected amino acids interacting with blebbistatin are green and in stick representation. (c) Identities of residues found in nonmuscle myosin IIA and IIB, skeletal myosin II, smooth muscle myosin II, and myosin Ib, V and X corresponding to selected residues in D. discoideum myosin II that interact with blebbistatin are shown. The level of inhibition is shown for each myosin form14.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 378-379) copyright 2005.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21079840 C.P.Lawson, A.M.Slawin, and N.J.Westwood (2011).
Application of the copper catalysed N-arylation of amidines in the synthesis of analogues of the chemical tool, blebbistatin.
  Chem Commun (Camb), 47, 1057-1059.  
21383151 E.M.Hur, I.H.Yang, D.H.Kim, J.Byun, Saijilafu, W.L.Xu, P.R.Nicovich, R.Cheong, A.Levchenko, N.Thakor, and F.Q.Zhou (2011).
Engineering neuronal growth cones to promote axon regeneration over inhibitory molecules.
  Proc Natl Acad Sci U S A, 108, 5057-5062.  
21102503 J.E.Bond, T.Q.Ho, M.A.Selim, C.L.Hunter, E.V.Bowers, and H.Levinson (2011).
Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodeling.
  Lab Invest, 91, 499-508.  
20351242 B.Takács, N.Billington, M.Gyimesi, B.Kintses, A.Málnási-Csizmadia, P.J.Knight, and M.Kovács (2010).
Myosin complexed with ADP and blebbistatin reversibly adopts a conformation resembling the start point of the working stroke.
  Proc Natl Acad Sci U S A, 107, 6799-6804.  
20332622 C.J.Jou, K.W.Spitzer, and M.Tristani-Firouzi (2010).
Blebbistatin effectively uncouples the excitation-contraction process in zebrafish embryonic heart.
  Cell Physiol Biochem, 25, 419-424.  
20404178 D.Yu, A.M.Marchiando, C.R.Weber, D.R.Raleigh, Y.Wang, L.Shen, and J.R.Turner (2010).
MLCK-dependent exchange and actin binding region-dependent anchoring of ZO-1 regulate tight junction barrier function.
  Proc Natl Acad Sci U S A, 107, 8237-8241.  
20459085 J.J.Frye, V.A.Klenchin, C.R.Bagshaw, and I.Rayment (2010).
Insights into the importance of hydrogen bonding in the gamma-phosphate binding pocket of myosin: structural and functional studies of serine 236.
  Biochemistry, 49, 4897-4907.
PDB codes: 3myh 3myk 3myl
20065948 J.Si, Y.Ge, S.Zhuang, and R.Gong (2010).
Inhibiting nonmuscle myosin II impedes inflammatory infiltration and ameliorates progressive renal disease.
  Lab Invest, 90, 448-458.  
20116385 M.Oleszczuk, I.M.Robertson, M.X.Li, and B.D.Sykes (2010).
Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: the basis of W7 as an inhibitor of cardiac muscle contraction.
  J Mol Cell Cardiol, 48, 925-933.
PDB code: 2krd
20025872 N.Lakshman, A.Kim, and W.M.Petroll (2010).
Characterization of corneal keratocyte morphology and mechanical activity within 3-D collagen matrices.
  Exp Eye Res, 90, 350-359.  
20564232 P.G.Flynn, and D.M.Helfman (2010).
Non-muscle myosin IIB helps mediate TNF cell death signaling independent of actomyosin contractility (AMC).
  J Cell Biochem, 110, 1365-1375.  
20566876 P.J.Hanley, Y.Xu, M.Kronlage, K.Grobe, P.Schön, J.Song, L.Sorokin, A.Schwab, and M.Bähler (2010).
Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility.
  Proc Natl Acad Sci U S A, 107, 12145-12150.  
20097204 S.Huke, and B.C.Knollmann (2010).
Increased myofilament Ca2+-sensitivity and arrhythmia susceptibility.
  J Mol Cell Cardiol, 48, 824-833.  
20165804 T.Saito, N.Furukawa, and T.Otani (2010).
A facile synthesis of pyrrolo[2,3-b]quinolines via a Rh(I)-catalyzed carbodiimide-Pauson-Khand-type reaction.
  Org Biomol Chem, 8, 1126-1132.  
20004664 Y.B.Sun, and M.Irving (2010).
The molecular basis of the steep force-calcium relation in heart muscle.
  J Mol Cell Cardiol, 48, 859-865.  
19420137 B.W.Doreian, T.G.Fulop, R.L.Meklemburg, and C.B.Smith (2009).
Cortical F-actin, the exocytic mode, and neuropeptide release in mouse chromaffin cells is regulated by myristoylated alanine-rich C-kinase substrate and myosin II.
  Mol Biol Cell, 20, 3142-3154.  
19109430 J.A.Brown, R.B.Wysolmerski, and P.C.Bridgman (2009).
Dorsal root ganglion neurons react to semaphorin 3A application through a biphasic response that requires multiple myosin II isoforms.
  Mol Biol Cell, 20, 1167-1179.  
19224562 K.M.Kollins, J.Hu, P.C.Bridgman, Y.Q.Huang, and G.Gallo (2009).
Myosin-II negatively regulates minor process extension and the temporal development of neuronal polarity.
  Dev Neurobiol, 69, 279-298.  
19167306 M.Linari, G.Piazzesi, and V.Lombardi (2009).
The effect of myofilament compliance on kinetics of force generation by myosin motors in muscle.
  Biophys J, 96, 583-592.  
19125340 M.Stewart, K.Franks-Skiba, and R.Cooke (2009).
Myosin regulatory light chain phosphorylation inhibits shortening velocities of skeletal muscle fibers in the presence of the myosin inhibitor blebbistatin.
  J Muscle Res Cell Motil, 30, 17-27.  
19282614 M.Watanabe, F.Kobirumaki, and M.Yumoto (2009).
[Direct regulation of contractile filaments: novel therapeutic strategy for vasospasm treatment]
  Nippon Yakurigaku Zasshi, 133, 130-133.  
19520847 N.Albet-Torres, M.J.Bloemink, T.Barman, R.Candau, K.Frölander, M.A.Geeves, K.Golker, C.Herrmann, C.Lionne, C.Piperio, S.Schmitz, C.Veigel, and A.Månsson (2009).
Drug effect unveils inter-head cooperativity and strain-dependent ADP release in fast skeletal actomyosin.
  J Biol Chem, 284, 22926-22937.  
19122661 R.Fedorov, M.Böhl, G.Tsiavaliaris, F.K.Hartmann, M.H.Taft, P.Baruch, B.Brenner, R.Martin, H.J.Knölker, H.O.Gutzeit, and D.J.Manstein (2009).
The mechanism of pentabromopseudilin inhibition of myosin motor activity.
  Nat Struct Mol Biol, 16, 80-88.
PDB codes: 2jhr 2jj9 3mjx
19413972 S.Xu, H.D.White, G.W.Offer, and L.C.Yu (2009).
Stabilization of helical order in the thick filaments by blebbistatin: further evidence of coexisting multiple conformations of myosin.
  Biophys J, 96, 3673-3681.  
19782397 Z.H.Syedain, J.Bjork, L.Sando, and R.T.Tranquillo (2009).
Controlled compaction with ruthenium-catalyzed photochemical cross-linking of fibrin-based engineered connective tissue.
  Biomaterials, 30, 6695-6701.  
17896341 B.Salhia, J.H.Hwang, C.A.Smith, M.Nakada, F.Rutka, M.Symons, and J.T.Rutka (2008).
Role of myosin II activity and the regulation of myosin light chain phosphorylation in astrocytomas.
  Cell Motil Cytoskeleton, 65, 12-24.  
18528569 C.Lucas-Lopez, J.S.Allingham, T.Lebl, C.P.Lawson, R.Brenk, J.R.Sellers, I.Rayment, and N.J.Westwood (2008).
The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design.
  Org Biomol Chem, 6, 2076-2084.
PDB codes: 3bz7 3bz8 3bz9
18765194 D.F.Stowe, A.K.Camara, J.S.Heisner, M.Aldakkak, and D.R.Harder (2008).
Low-flow perfusion of guinea pig isolated hearts with 26 degrees C air-saturated Lifor solution for 20 hours preserves function and metabolism.
  J Heart Lung Transplant, 27, 1008-1015.  
18773891 F.K.Fulcher, B.T.Smith, M.Russ, and Y.M.Patel (2008).
Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes.
  Exp Cell Res, 314, 3264-3274.  
18599626 F.Q.Zhao, R.Padrón, and R.Craig (2008).
Blebbistatin stabilizes the helical order of myosin filaments by promoting the switch 2 closed state.
  Biophys J, 95, 3322-3329.  
17994251 G.P.Farman, K.Tachampa, R.Mateja, O.Cazorla, A.Lacampagne, and P.P.de Tombe (2008).
Blebbistatin: use as inhibitor of muscle contraction.
  Pflugers Arch, 455, 995.  
18155233 J.H.Brown, Y.Yang, L.Reshetnikova, S.Gourinath, D.Süveges, J.Kardos, F.Hóbor, R.Reutzel, L.Nyitray, and C.Cohen (2008).
An unstable head-rod junction may promote folding into the compact off-state conformation of regulated myosins.
  J Mol Biol, 375, 1434-1443.
PDB codes: 3bas 3bat
18195072 N.A.Morin, P.W.Oakes, Y.M.Hyun, D.Lee, E.Y.Chin, M.R.King, T.A.Springer, M.Shimaoka, J.X.Tang, J.S.Reichner, and M.Kim (2008).
Nonmuscle myosin heavy chain IIAmediates integrin LFA-1 de-adhesion during T lymphocyte migration.
  J Exp Med, 205, 195-205.  
19039672 S.Galler (2008).
Molecular basis of the catch state in molluscan smooth muscles: a catchy challenge.
  J Muscle Res Cell Motil, 29, 73-99.  
18642125 V.Y.Sidorov, M.R.Holcomb, M.C.Woods, R.A.Gray, and J.P.Wikswo (2008).
Effects of unipolar stimulation on voltage and calcium distributions in the isolated rabbit heart.
  Basic Res Cardiol, 103, 537-551.  
18452153 W.M.Petroll, L.Ma, A.Kim, L.Ly, and M.Vishwanath (2008).
Dynamic assessment of fibroblast mechanical activity during Rac-induced cell spreading in 3-D culture.
  J Cell Physiol, 217, 162-171.  
18701651 Z.M.Goeckeler, P.C.Bridgman, and R.B.Wysolmerski (2008).
Nonmuscle myosin II is responsible for maintaining endothelial cell basal tone and stress fiber integrity.
  Am J Physiol Cell Physiol, 295, C994-1006.  
17488351 G.J.Johnson, L.A.Leis, M.D.Krumwiede, and J.G.White (2007).
The critical role of myosin IIA in platelet internal contraction.
  J Thromb Haemost, 5, 1516-1529.  
17645784 S.D.Calaminus, J.M.Auger, O.J.McCarty, M.J.Wakelam, L.M.Machesky, and S.P.Watson (2007).
MyosinIIa contractility is required for maintenance of platelet structure during spreading on collagen and contributes to thrombus stability.
  J Thromb Haemost, 5, 2136-2145.  
17900617 S.Tang, J.C.Liao, A.R.Dunn, R.B.Altman, J.A.Spudich, and J.P.Schmidt (2007).
Predicting allosteric communication in myosin via a pathway of conserved residues.
  J Mol Biol, 373, 1361-1373.  
16923388 A.J.Engler, S.Sen, H.L.Sweeney, and D.E.Discher (2006).
Matrix elasticity directs stem cell lineage specification.
  Cell, 126, 677-689.  
17094935 K.A.Beningo, K.Hamao, M.Dembo, Y.L.Wang, and H.Hosoya (2006).
Traction forces of fibroblasts are regulated by the Rho-dependent kinase but not by the myosin light chain kinase.
  Arch Biochem Biophys, 456, 224-231.  
16501565 N.A.Medeiros, D.T.Burnette, and P.Forscher (2006).
Myosin II functions in actin-bundle turnover in neuronal growth cones.
  Nat Cell Biol, 8, 215-226.  
16642020 R.M.Toydemir, A.Rutherford, F.G.Whitby, L.B.Jorde, J.C.Carey, and M.J.Bamshad (2006).
Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome.
  Nat Genet, 38, 561-565.  
16473905 T.M.Butler, S.U.Mooers, and M.J.Siegman (2006).
Catch force links and the low to high force transition of myosin.
  Biophys J, 90, 3193-3202.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.