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PDBsum entry 1qz6
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Structural protein PDB id
1qz6

 

 

 

 

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Contents
Protein chain
360 a.a.
Ligands
GLC-FRU
ATP
JAS
Metals
_CA
Waters ×274
PDB id:
1qz6
Name: Structural protein
Title: Structure of rabbit actin in complex with jaspisamide a
Structure: Actin, alpha skeletal muscle. Chain: a. Synonym: alpha-actin 1
Source: Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986
Resolution:
1.60Å     R-factor:   0.167     R-free:   0.197
Authors: V.A.Klenchin,J.S.Allingham,R.King,J.Tanaka,G.Marriott,I.Rayment
Key ref:
V.A.Klenchin et al. (2003). Trisoxazole macrolide toxins mimic the binding of actin-capping proteins to actin. Nat Struct Biol, 10, 1058-1063. PubMed id: 14578936 DOI: 10.1038/nsb1006
Date:
15-Sep-03     Release date:   11-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P68135  (ACTS_RABIT) -  Actin, alpha skeletal muscle from Oryctolagus cuniculus
Seq:
Struc: 		377 a.a.
360 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1038/nsb1006 Nat Struct Biol 10:1058-1063 (2003)
PubMed id: 14578936  
 
 
Trisoxazole macrolide toxins mimic the binding of actin-capping proteins to actin.
V.A.Klenchin, J.S.Allingham, R.King, J.Tanaka, G.Marriott, I.Rayment.
 
  ABSTRACT  
 
Marine macrolide toxins of trisoxazole family target actin with high affinity and specificity and have promising pharmacological properties. We present X-ray structures of actin in complex with two members of this family, kabiramide C and jaspisamide A, at a resolution of 1.45 and 1.6 A, respectively. The structures reveal the absolute stereochemistry of these toxins and demonstrate that their trisoxazole ring interacts with actin subdomain 1 while the aliphatic side chain is inserted into the hydrophobic cavity between actin subdomains 1 and 3. The binding site is essentially the same as the one occupied by the actin-capping domain of the gelsolin superfamily of proteins. The structural evidence suggests that actin filament severing and capping by these toxins is also analogous to that of gelsolin. Consequently, these macrolides may be viewed as small molecule biomimetics of an entire class of actin-binding proteins.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Trisoxazole-containing macrolide toxins bind to the same site on actin as gelsolin domain 1. (a) The structure of the actin -jaspisamide A complex in two orientations where actin is depicted in a ribbon representation and the toxin is shown as a space-filling model in red. Actin subdomains 1 -4 are labeled. (b) A space-filling representation of the residues on actin that interact with kabiramide C (left) and gelsolin domain 1 (right). The coordinates for gelsolin domain 1 were obtained from the RCSB (PDB entry 1EQY)5, 6. (c) Overlay of kabiramide C (red, space-filling representation) and gelsolin domain 1 (blue) based on the superposition of the actin in their respective complexes. For gelsolin domain 1 the actin-binding helix, Ser70 -Leu88, is shown in space-filling representation. (d) Kabiramide C binding site on actin. Toxin is shown as ball and stick representation in cyan; labeled amino acid residues contacting kabiramide C are shown in CPK colors as a space-filling model. 		Figure 3.
Figure 3. Kabiramide C binding to the actin filament may result in steric clashes with the neighboring actin subunit. Kabiramide C in G-actin-bound conformation (red) is superimposed onto the model for F-actin31, 33. For clarity, four actin subunits are depicted where the filament axis is vertical with the barbed end at the bottom. The two in the front, shown in blue and green, reveal the location of kabiramide between longitudinally contacting actin monomers.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 1058-1063) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21550239 S.C.Chung, S.H.Lee, K.H.Jang, W.Park, J.E.Jeon, H.Oh, J.Shin, and K.B.Oh (2011).
Actin depolymerizing effect of trisoxazole-containing macrolides.
  Bioorg Med Chem Lett, 21, 3198-3201.  
20971629 A.E.Wright (2010).
The Lithistida: important sources of compounds useful in biomedical research.
  Curr Opin Biotechnol, 21, 801-807.  
20797609 J.C.Blain, Y.F.Mok, J.Kubanek, and J.S.Allingham (2010).
Two molecules of lobophorolide cooperate to stabilize an actin dimer using both their "ring" and "tail" region.
  Chem Biol, 17, 802-807.
PDB code: 3m6g
20946985 K.Murakami, T.Yasunaga, T.Q.Noguchi, Y.Gomibuchi, K.X.Ngo, T.Q.Uyeda, and T.Wakabayashi (2010).
Structural basis for actin assembly, activation of ATP hydrolysis, and delayed phosphate release.
  Cell, 143, 275-287.
PDB codes: 3a5l 3a5m 3a5n 3a5o 3g37
19254038 D.S.Dalisay, E.W.Rogers, A.S.Edison, and T.F.Molinski (2009).
Structure elucidation at the nanomole scale. 1. Trisoxazole macrolides and thiazole-containing cyclic peptides from the nudibranch Hexabranchus sanguineus.
  J Nat Prod, 72, 732-738.  
19489598 T.L.Simmons, L.M.Nogle, J.Media, F.A.Valeriote, S.L.Mooberry, and W.H.Gerwick (2009).
Desmethoxymajusculamide C, a cyanobacterial depsipeptide with potent cytotoxicity in both cyclic and ring-opened forms.
  J Nat Prod, 72, 1011-1016.  
17951576 D.S.Kudryashov, C.L.Cordero, E.Reisler, and K.J.Satchell (2008).
Characterization of the enzymatic activity of the actin cross-linking domain from the Vibrio cholerae MARTX Vc toxin.
  J Biol Chem, 283, 445-452.  
18945676 E.Stokasimov, M.McKane, and P.A.Rubenstein (2008).
Role of intermonomer ionic bridges in the stabilization of the actin filament.
  J Biol Chem, 283, 34844-34854.  
18663717 H.J.Chen, W.L.Wang, G.F.Wang, L.P.Shi, M.Gu, Y.D.Ren, L.F.Hou, P.L.He, F.H.Zhu, X.G.Zhong, W.Tang, J.P.Zuo, and F.J.Nan (2008).
Rational design and synthesis of 2,2-bisheterocycle tandem derivatives as non-nucleoside hepatitis B virus inhibitors.
  ChemMedChem, 3, 1316-1321.  
18355717 J.Tanaka, J.C.Blain, and J.S.Allingham (2008).
Actin-binding toxin "tail" wags the dog.
  Chem Biol, 15, 205-207.  
18689676 K.Baek, X.Liu, F.Ferron, S.Shu, E.D.Korn, and R.Dominguez (2008).
Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding.
  Proc Natl Acad Sci U S A, 105, 11748-11753.
PDB codes: 3chw 3ci5 3cip
18391412 M.R.Sawaya, D.S.Kudryashov, I.Pashkov, H.Adisetiyo, E.Reisler, and T.O.Yeates (2008).
Multiple crystal structures of actin dimers and their implications for interactions in the actin filament.
  Acta Crystallogr D Biol Crystallogr, 64, 454-465.
PDB codes: 2q1n 2q31 2q36
18355728 R.D.Perrins, G.Cecere, I.Paterson, and G.Marriott (2008).
Synthetic mimetics of actin-binding macrolides: rational design of actin-targeted drugs.
  Chem Biol, 15, 287-294.  
18938176 U.B.Nair, P.B.Joel, Q.Wan, S.Lowey, M.A.Rould, and K.M.Trybus (2008).
Crystal structures of monomeric actin bound to cytochalasin D.
  J Mol Biol, 384, 848-864.
PDB codes: 3eks 3eku 3el2
17994018 D.C.Guo, H.Pannu, V.Tran-Fadulu, C.L.Papke, R.K.Yu, N.Avidan, S.Bourgeois, A.L.Estrera, H.J.Safi, E.Sparks, D.Amor, L.Ades, V.McConnell, C.E.Willoughby, D.Abuelo, M.Willing, R.A.Lewis, D.H.Kim, S.Scherer, P.P.Tung, C.Ahn, L.M.Buja, C.S.Raman, S.S.Shete, and D.M.Milewicz (2007).
Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.
  Nat Genet, 39, 1488-1493.  
17351011 J.L.Melville, I.H.Moal, C.Baker-Glenn, P.E.Shaw, G.Pattenden, and J.D.Hirst (2007).
The structural determinants of macrolide-actin binding: in silico insights.
  Biophys J, 92, 3862-3867.  
17599353 J.S.Allingham, C.O.Miles, and I.Rayment (2007).
A structural basis for regulation of actin polymerization by pectenotoxins.
  J Mol Biol, 371, 959-970.
PDB codes: 2q0r 2q0u
16757474 A.Pelikan Conchaudron, D.Didry, K.H.Le, E.Larquet, N.Boisset, D.Pantaloni, and M.F.Carlier (2006).
Analysis of tetramethylrhodamine-labeled actin polymerization and interaction with actin regulatory proteins.
  J Biol Chem, 281, 24036-24047.  
16689636 K.Takamoto, and M.R.Chance (2006).
Radiolytic protein footprinting with mass spectrometry to probe the structure of macromolecular complexes.
  Annu Rev Biophys Biomol Struct, 35, 251-276.  
16920713 M.A.Rould, Q.Wan, P.B.Joel, S.Lowey, and K.M.Trybus (2006).
Crystal structures of expressed non-polymerizable monomeric actin in the ADP and ATP states.
  J Biol Chem, 281, 31909-31919.
PDB codes: 2hf3 2hf4
16773128 N.D.Rendtorff, M.Zhu, T.Fagerheim, T.L.Antal, M.Jones, T.M.Teslovich, E.M.Gillanders, M.Barmada, E.Teig, J.M.Trent, K.H.Friderici, D.A.Stephan, and L.Tranebjaerg (2006).
A novel missense mutation in ACTG1 causes dominant deafness in a Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among families with hereditary hearing impairment.
  Eur J Hum Genet, 14, 1097-1105.  
16428279 T.J.Minehardt, P.A.Kollman, R.Cooke, and E.Pate (2006).
The open nucleotide pocket of the profilin/actin x-ray structure is unstable and closes in the absence of profilin.
  Biophys J, 90, 2445-2449.  
15741975 A.H.Aguda, L.D.Burtnick, and R.C.Robinson (2005).
The state of the filament.
  EMBO Rep, 6, 220-226.  
16372404 A.V.Statsuk, R.Bai, J.L.Baryza, V.A.Verma, E.Hamel, P.A.Wender, and S.A.Kozmin (2005).
Actin is the primary cellular receptor of bistramide A.
  Nat Chem Biol, 1, 383-388.  
16141336 D.S.Kudryashov, M.R.Sawaya, H.Adisetiyo, T.Norcross, G.Hegyi, E.Reisler, and T.O.Yeates (2005).
The crystal structure of a cross-linked actin dimer suggests a detailed molecular interface in F-actin.
  Proc Natl Acad Sci U S A, 102, 13105-13110.
PDB code: 2a5x
15934040 G.Aldini, I.Dalle-Donne, G.Vistoli, R.Maffei Facino, and M.Carini (2005).
Covalent modification of actin by 4-hydroxy-trans-2-nonenal (HNE): LC-ESI-MS/MS evidence for Cys374 Michael adduction.
  J Mass Spectrom, 40, 946-954.  
16192358 J.S.Allingham, A.Zampella, M.V.D'Auria, and I.Rayment (2005).
Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity.
  Proc Natl Acad Sci U S A, 102, 14527-14532.
PDB codes: 2asm 2aso 2asp
15939738 M.Barzik, T.I.Kotova, H.N.Higgs, L.Hazelwood, D.Hanein, F.B.Gertler, and D.A.Schafer (2005).
Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins.
  J Biol Chem, 280, 28653-28662.  
15505213 B.J.Nolen, R.S.Littlefield, and T.D.Pollard (2004).
Crystal structures of actin-related protein 2/3 complex with bound ATP or ADP.
  Proc Natl Acad Sci U S A, 101, 15627-15632.
PDB codes: 1tyq 1u2v
15201432 I.Paterson, R.Britton, K.Ashton, H.Knust, and J.Stafford (2004).
Synthesis of antimicrofilament marine macrolides: synthesis and configurational assignment of a C5-C16 degradation fragment of reidispongiolide A.
  Proc Natl Acad Sci U S A, 101, 11986-11991.  
15539076 J.Moyersoen, J.Choe, E.Fan, W.G.Hol, and P.A.Michels (2004).
Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target.
  FEMS Microbiol Rev, 28, 603-643.  
15215896 L.D.Burtnick, D.Urosev, E.Irobi, K.Narayan, and R.C.Robinson (2004).
Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF.
  EMBO J, 23, 2713-2722.
PDB code: 1rgi
15501675 R.Dominguez (2004).
Actin-binding proteins--a unifying hypothesis.
  Trends Biochem Sci, 29, 572-578.  
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 code is shown on the right.

 

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