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PDBsum entry 3e22

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protein ligands metals Protein-protein interface(s) links
Cell cycle PDB id
3e22
Jmol
Contents
Protein chains
427 a.a. *
419 a.a. *
124 a.a. *
Ligands
GTP ×2
GDP ×2
LOC ×2
TZT
Metals
_MG ×2
* Residue conservation analysis
PDB id:
3e22
Name: Cell cycle
Title: Tubulin-colchicine-soblidotin: stathmin-like domain complex
Structure: Tubulin alpha-1c chain. Chain: a, c. Synonym: tubulin alpha chain. Tubulin beta-2b chain. Chain: b, d. Synonym: tubulin beta chain. Stathmin-4. Chain: e. Fragment: rb3 stathmin-like domain 4.
Source: Bos taurus. Bovine. Organism_taxid: 9913. Organ: brain. Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: stmn4. Expressed in: escherichia coli.
Resolution:
3.80Å     R-factor:   0.231     R-free:   0.295
Authors: A.Cormier,M.Marchand,R.B.Ravelli,M.Knossow,B.Gigant
Key ref: A.Cormier et al. (2008). Structural insight into the inhibition of tubulin by vinca domain peptide ligands. EMBO Rep, 9, 1101-1106. PubMed id: 18787557
Date:
05-Aug-08     Release date:   21-Oct-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q3ZCJ7  (TBA1C_BOVIN) -  Tubulin alpha-1C chain
Seq:
Struc:
449 a.a.
427 a.a.
Protein chains
Pfam   ArchSchema ?
Q6B856  (TBB2B_BOVIN) -  Tubulin beta-2B chain
Seq:
Struc:
445 a.a.
419 a.a.*
Protein chain
Pfam   ArchSchema ?
P63043  (STMN4_RAT) -  Stathmin-4
Seq:
Struc:
189 a.a.
124 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   5 terms 
  Biological process     microtubule-based process   5 terms 
  Biochemical function     nucleotide binding     4 terms  

 

 
EMBO Rep 9:1101-1106 (2008)
PubMed id: 18787557  
 
 
Structural insight into the inhibition of tubulin by vinca domain peptide ligands.
A.Cormier, M.Marchand, R.B.Ravelli, M.Knossow, B.Gigant.
 
  ABSTRACT  
 
The tubulin vinca domain is the target of widely different microtubule inhibitors that interfere with the binding of vinblastine. Although all these ligands inhibit the hydrolysis of GTP, they affect nucleotide exchange to variable extents. The structures of two vinca domain antimitotic peptides--phomopsin A and soblidotin (a dolastatin 10 analogue)--bound to tubulin in a complex with a stathmin-like domain show that their sites partly overlap with that of vinblastine and extend the definition of the vinca domain. The structural data, together with the biochemical results from the ligands we studied, highlight two main contributors in nucleotide exchange: the flexibility of the tubulin subunits' arrangement at their interfaces and the residues in the carboxy-terminal part of the beta-tubulin H6-H7 loop. The structures also highlight common features of the mechanisms by which vinca domain ligands favour curved tubulin assemblies and destabilize microtubules.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21381049 R.A.Stanton, K.M.Gernert, J.H.Nettles, and R.Aneja (2011).
Drugs that target dynamic microtubules: a new molecular perspective.
  Med Res Rev, 31, 443-481.  
20885410 C.Dumontet, and M.A.Jordan (2010).
Microtubule-binding agents: a dynamic field of cancer therapeutics.
  Nat Rev Drug Discov, 9, 790-803.  
20107862 D.Calligaris, P.Verdier-Pinard, F.Devred, C.Villard, D.Braguer, and D.Lafitte (2010).
Microtubule targeting agents: from biophysics to proteomics.
  Cell Mol Life Sci, 67, 1089-1104.  
20030375 J.A.Smith, L.Wilson, O.Azarenko, X.Zhu, B.M.Lewis, B.A.Littlefield, and M.A.Jordan (2010).
Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability.
  Biochemistry, 49, 1331-1337.  
19131341 A.Cormier, M.J.Clément, M.Knossow, S.Lachkar, P.Savarin, F.Toma, A.Sobel, B.Gigant, and P.A.Curmi (2009).
The PN2-3 domain of centrosomal P4.1-associated protein implements a novel mechanism for tubulin sequestration.
  J Biol Chem, 284, 6909-6917.  
19666559 A.Dorléans, B.Gigant, R.B.Ravelli, P.Mailliet, V.Mikol, and M.Knossow (2009).
Variations in the colchicine-binding domain provide insight into the structural switch of tubulin.
  Proc Natl Acad Sci U S A, 106, 13775-13779.
PDB codes: 3hkb 3hkc 3hkd 3hke
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.