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PDBsum entry 1a1u

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protein Protein-protein interface(s) links
Anti-oncogene PDB id
1a1u
Jmol
Contents
Protein chains
29 a.a. *
* Residue conservation analysis
PDB id:
1a1u
Name: Anti-oncogene
Title: Solution structure determination of a p53 mutant dimerization domain, nmr, minimized average structure
Structure: P53. Chain: a, c. Fragment: oligomerization. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: p53 tumor suppressor. Expressed in: escherichia coli. Expression_system_taxid: 562
NMR struc: 1 models
Authors: M.A.Mccoy,E.S.Stavridi,J.L.F.Waterman,A.Wieczorek, S.J.Opella,T.D.Halezonetis
Key ref:
M.McCoy et al. (1997). Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain. EMBO J, 16, 6230-6236. PubMed id: 9321402 DOI: 10.1093/emboj/16.20.6230
Date:
16-Dec-97     Release date:   08-Apr-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04637  (P53_HUMAN) -  Cellular tumor antigen p53
Seq:
Struc:
393 a.a.
29 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     apoptotic process   3 terms 
  Biochemical function     DNA binding     2 terms  

 

 
DOI no: 10.1093/emboj/16.20.6230 EMBO J 16:6230-6236 (1997)
PubMed id: 9321402  
 
 
Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain.
M.McCoy, E.S.Stavridi, J.L.Waterman, A.M.Wieczorek, S.J.Opella, T.D.Halazonetis.
 
  ABSTRACT  
 
The p53 tumor suppressor oligomerization domain, a dimer of two primary dimers, is an independently folding domain whose subunits consist of a beta-strand, a tight turn and an alpha-helix. To evaluate the effect of hydrophobic side-chains on three-dimensional structure, we substituted residues Phe341 and Leu344 in the alpha-helix with other hydrophobic amino acids. Substitutions that resulted in residue 341 having a smaller side-chain than residue 344 switched the stoichiometry of the domain from tetrameric to dimeric. The three-dimensional structure of one such dimer was determined by multidimensional NMR spectroscopy. When compared with the primary dimer of the wild-type p53 oligomerization domain, the mutant dimer showed a switch in alpha-helical packing from anti-parallel to parallel and rotation of the alpha-helices relative to the beta-strands. Hydrophobic side-chain size is therefore an important determinant of a protein fold.
 
  Selected figure(s)  
 
Figure 5.
Figure 5 Superimposition of 30 simulated annealing structures corresponding to residues 327–353 of human p53. Color hue distinguishes the two subunits.
Figure 6.
Figure 6 Orthogonal views of the p53KIY oligomerization domain corresponding to residues 327–353 of human p53. Color saturation and the presence or absence of a prime following the residue number distinguish the two subunits. Residue numbers followed by an asterisk refer to both subunits.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 6230-6236) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19121375 L.A.Holbrook, R.A.Butler, R.E.Cashon, and R.J.Van Beneden (2009).
Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53.
  Gene, 433, 81-87.  
18410249 A.C.Joerger, and A.R.Fersht (2008).
Structural biology of the tumor suppressor p53.
  Annu Rev Biochem, 77, 557-582.  
18345875 E.H.Rubensson, N.Bock, E.Holmström, and A.M.Niklasson (2008).
Recursive inverse factorization.
  J Chem Phys, 128, 104105.  
18076077 P.Mora, R.J.Carbajo, A.Pineda-Lucena, M.M.Sánchez del Pino, and E.Pérez-Payá (2008).
Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53--a structural and combinatorial approach.
  Proteins, 71, 1670-1685.
PDB codes: 2j0z 2j10 2j11
17581633 H.D.Ou, F.Löhr, V.Vogel, W.Mäntele, and V.Dötsch (2007).
Structural evolution of C-terminal domains in the p53 family.
  EMBO J, 26, 3463-3473.
PDB codes: 2rp4 2rp5
20141510 J.Deng, R.Dayam, and N.Neamati (2006).
Patented small molecule inhibitors of p53-MDM2 interaction.
  Expert Opin Ther Pat, 16, 165-188.  
16260757 C.Galea, P.Bowman, and R.W.Kriwacki (2005).
Disruption of an intermonomer salt bridge in the p53 tetramerization domain results in an increased propensity to form amyloid fibrils.
  Protein Sci, 14, 2993-3003.  
15509798 K.G.McLure, M.Takagi, and M.B.Kastan (2004).
NAD+ modulates p53 DNA binding specificity and function.
  Mol Cell Biol, 24, 9958-9967.  
12897847 E.Kim, and W.Deppert (2003).
The complex interactions of p53 with target DNA: we learn as we go.
  Biochem Cell Biol, 81, 141-150.  
12433927 R.D.Brokx, E.Bolewska-Pedyczak, and J.Gariépy (2003).
A stable human p53 heterotetramer based on constructive charge interactions within the tetramerization domain.
  J Biol Chem, 278, 2327-2332.  
12487430 G.Varadi, and L.Otvos (2002).
Synthesis of complex phosphopeptides as mimics of p53 functional domains.
  J Pept Sci, 8, 621-633.  
11592056 E.Matsumoto, T.Kiyota, S.Lee, G.Sugihara, S.Yamashita, H.Meno, Y.Aso, H.Sakamoto, and H.M.Ellerby (2000).
Study on the packing geometry, stoichiometry, and membrane interaction of three analogs related to a pore-forming small globular protein.
  Biopolymers, 56, 96.  
10341712 C.Prives, and P.A.Hall (1999).
The p53 pathway.
  J Pathol, 187, 112-126.  
  10493578 E.S.Stavridi, N.H.Chehab, L.C.Caruso, and T.D.Halazonetis (1999).
Change in oligomerization specificity of the p53 tetramerization domain by hydrophobic amino acid substitutions.
  Protein Sci, 8, 1773-1779.  
9582268 M.G.Mateu, and A.R.Fersht (1998).
Nine hydrophobic side chains are key determinants of the thermodynamic stability and oligomerization status of tumour suppressor p53 tetramerization domain.
  EMBO J, 17, 2748-2758.  
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.