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PDBsum entry 1ba6

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protein links
Glycoprotein PDB id
1ba6
Jmol
Contents
Protein chain
40 a.a. *
* Residue conservation analysis
PDB id:
1ba6
Name: Glycoprotein
Title: Solution structure of the methionine-oxidized amyloid beta- peptide (1-40). Does oxidation affect conformational switching? nmr, 10 structures
Structure: Amyloid beta-peptide. Chain: a. Fragment: abeta. Engineered: yes. Mutation: yes. Other_details: methionine oxidized
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: unidentified. Expression_system_taxid: 32644
NMR struc: 10 models
Authors: A.A.Watson,D.P.Fairlie,D.J.Craik
Key ref:
A.A.Watson et al. (1998). Solution structure of methionine-oxidized amyloid beta-peptide (1-40). Does oxidation affect conformational switching? Biochemistry, 37, 12700-12706. PubMed id: 9737846 DOI: 10.1021/bi9810757
Date:
22-Apr-98     Release date:   17-Jun-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05067  (A4_HUMAN) -  Amyloid beta A4 protein
Seq:
Struc:
 
Seq:
Struc:
770 a.a.
40 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     nervous system development   1 term 

 

 
DOI no: 10.1021/bi9810757 Biochemistry 37:12700-12706 (1998)
PubMed id: 9737846  
 
 
Solution structure of methionine-oxidized amyloid beta-peptide (1-40). Does oxidation affect conformational switching?
A.A.Watson, D.P.Fairlie, D.J.Craik.
 
  ABSTRACT  
 
The solution structure of Abeta(1-40)Met(O), the methionine-oxidized form of amyloid beta-peptide Abeta(1-40), has been investigated by CD and NMR spectroscopy. Oxidation of Met35 may have implications in the aetiology of Alzheimer's disease. Circular dichroism experiments showed that whereas Abeta(1-40) and Abeta(1-40)Met(O) both adopt essentially random coil structures in water (pH 4) at micromolar concentrations, the former aggregates within several days while the latter is stable for at least 7 days under these conditions. This remarkable difference led us to determine the solution structure of Abeta(1-40)Met(O) using 1H NMR spectroscopy. In a water-SDS micelle medium needed to solubilize both peptides at the millimolar concentrations required to measure NMR spectra, chemical shift and NOE data for Abeta(1-40)Met(O) strongly suggest the presence of a helical region between residues 16 and 24. This is supported by slow H-D exchange of amide protons in this region and by structure calculations using simulated annealing with the program XPLOR. The remainder of the structure is relatively disordered. Our previously reported NMR data for Abeta(1-40) in the same solvent shows that helices are present over residues 15-24 (helix 1) and 28-36 (helix 2). Oxidation of Met35 thus causes a local and selective disruption of helix 2. In addition to this helix-coil rearrangement in aqueous micelles, the CD data show that oxidation inhibits a coil-to-beta-sheet transition in water. These significant structural rearrangements in the C-terminal region of Abeta may be important clues to the chemistry and biology of Abeta(1-40) and Abeta(1-42).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21044048 P.Maiti, R.Piacentini, C.Ripoli, C.Grassi, and G.Bitan (2010).
Surprising toxicity and assembly behaviour of amyloid β-protein oxidized to sulfone.
  Biochem J, 433, 323-332.  
18058241 E.Nordling, Y.Kallberg, J.Johansson, and B.Persson (2008).
Molecular dynamics studies of alpha-helix stability in fibril-forming peptides.
  J Comput Aided Mol Des, 22, 53-58.  
  18453721 K.S.Wun, L.A.Miles, G.A.Crespi, K.Wycherley, D.B.Ascher, K.J.Barnham, R.Cappai, K.Beyreuther, C.L.Masters, M.W.Parker, and W.J.McKinstry (2008).
Crystallization and preliminary X-ray diffraction analysis of the Fab fragment of WO2, an antibody specific for the Abeta peptides associated with Alzheimer's disease.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 438-441.  
18228239 M.Valerio, F.Porcelli, J.P.Zbilut, A.Giuliani, C.Manetti, and F.Conti (2008).
pH effects on the conformational preferences of amyloid beta-peptide (1-40) in HFIP aqueous solution by NMR spectroscopy.
  ChemMedChem, 3, 833-843.  
17413657 A.S.Johansson, J.Bergquist, C.Volbracht, A.Päiviö, M.Leist, L.Lannfelt, and A.Westlind-Danielsson (2007).
Attenuated amyloid-beta aggregation and neurotoxicity owing to methionine oxidation.
  Neuroreport, 18, 559-563.  
17211889 F.Dulin, I.Callebaut, N.Colloc'h, and J.P.Mornon (2007).
Sequence-based modeling of Abeta42 soluble oligomers.
  Biopolymers, 85, 422-437.  
17525469 J.Meinhardt, G.G.Tartaglia, A.Pawar, T.Christopeit, P.Hortschansky, V.Schroeckh, C.M.Dobson, M.Vendruscolo, and M.Fändrich (2007).
Similarities in the thermodynamics and kinetics of aggregation of disease-related Abeta(1-40) peptides.
  Protein Sci, 16, 1214-1222.  
17402723 M.P.Samant, R.White, D.J.Hong, G.Croston, P.M.Conn, J.A.Janovick, and J.Rivier (2007).
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
  J Med Chem, 50, 2067-2077.  
17307823 S.Yun, B.Urbanc, L.Cruz, G.Bitan, D.B.Teplow, and H.E.Stanley (2007).
Role of electrostatic interactions in amyloid beta-protein (A beta) oligomer formation: a discrete molecular dynamics study.
  Biophys J, 92, 4064-4077.  
17456743 S.Zibaee, O.S.Makin, M.Goedert, and L.C.Serpell (2007).
A simple algorithm locates beta-strands in the amyloid fibril core of alpha-synuclein, Abeta, and tau using the amino acid sequence alone.
  Protein Sci, 16, 906-918.  
16826550 J.Danielsson, A.Andersson, J.Jarvet, and A.Gräslund (2006).
15N relaxation study of the amyloid beta-peptide: structural propensities and persistence length.
  Magn Reson Chem, 44, S114-S121.  
17215879 J.K.Rainey, L.Fliegel, and B.D.Sykes (2006).
Strategies for dealing with conformational sampling in structural calculations of flexible or kinked transmembrane peptides.
  Biochem Cell Biol, 84, 918-929.  
16987248 P.J.Crouch, K.J.Barnham, J.A.Duce, R.E.Blake, C.L.Masters, and I.A.Trounce (2006).
Copper-dependent inhibition of cytochrome c oxidase by Abeta(1-42) requires reduced methionine at residue 35 of the Abeta peptide.
  J Neurochem, 99, 226-236.  
17073452 S.Abu-Baker, and G.A.Lorigan (2006).
Phospholamban and its phosphorylated form interact differently with lipid bilayers: a 31P, 2H, and 13C solid-state NMR spectroscopic study.
  Biochemistry, 45, 13312-13322.  
16809342 Y.R.Chen, and C.G.Glabe (2006).
Distinct early folding and aggregation properties of Alzheimer amyloid-beta peptides Abeta40 and Abeta42: stable trimer or tetramer formation by Abeta42.
  J Biol Chem, 281, 24414-24422.  
17191956 G.L.Teper, L.Lecanu, J.Greeson, and V.Papadopoulos (2005).
Methodology for multi-site ligand-protein docking identification developed for the optimization of spirostenol inhibition of beta-amyloid-induced neurotoxicity.
  Chem Biodivers, 2, 1571-1579.  
15930005 N.D.Lazo, M.A.Grant, M.C.Condron, A.C.Rigby, and D.B.Teplow (2005).
On the nucleation of amyloid beta-protein monomer folding.
  Protein Sci, 14, 1581-1596.  
16199659 P.Hortschansky, T.Christopeit, V.Schroeckh, and M.Fändrich (2005).
Thermodynamic analysis of the aggregation propensity of oxidized Alzheimer's beta-amyloid variants.
  Protein Sci, 14, 2915-2918.  
15987892 T.Christopeit, P.Hortschansky, V.Schroeckh, K.Gührs, G.Zandomeneghi, and M.Fändrich (2005).
Mutagenic analysis of the nucleation propensity of oxidized Alzheimer's beta-amyloid peptide.
  Protein Sci, 14, 2125-2131.  
15096631 A.Päiviö, E.Nordling, Y.Kallberg, J.Thyberg, and J.Johansson (2004).
Stabilization of discordant helices in amyloid fibril-forming proteins.
  Protein Sci, 13, 1251-1259.  
15649580 C.Morgan, M.Colombres, M.T.Nuñez, and N.C.Inestrosa (2004).
Structure and function of amyloid in Alzheimer's disease.
  Prog Neurobiol, 74, 323-349.  
15272266 E.Bossy-Wetzel, R.Schwarzenbacher, and S.A.Lipton (2004).
Molecular pathways to neurodegeneration.
  Nat Med, 10, S2-S9.  
15203119 M.E.Clementi, G.E.Martorana, M.Pezzotti, B.Giardina, and F.Misiti (2004).
Methionine 35 oxidation reduces toxic effects of the amyloid beta-protein fragment (31-35) on human red blood cell.
  Int J Biochem Cell Biol, 36, 2066-2076.  
12925530 K.J.Barnham, G.D.Ciccotosto, A.K.Tickler, F.E.Ali, D.G.Smith, N.A.Williamson, Y.H.Lam, D.Carrington, D.Tew, G.Kocak, I.Volitakis, F.Separovic, C.J.Barrow, J.D.Wade, C.L.Masters, R.A.Cherny, C.C.Curtain, A.I.Bush, and R.Cappai (2003).
Neurotoxic, redox-competent Alzheimer's beta-amyloid is released from lipid membrane by methionine oxidation.
  J Biol Chem, 278, 42959-42965.  
12031904 J.Kanski, M.Aksenova, C.Schöneich, and D.A.Butterfield (2002).
Substitution of isoleucine-31 by helical-breaking proline abolishes oxidative stress and neurotoxic properties of Alzheimer's amyloid beta-peptide.
  Free Radic Biol Med, 32, 1205-1211.  
12198111 L.Hou, I.Kang, R.E.Marchant, and M.G.Zagorski (2002).
Methionine 35 oxidation reduces fibril assembly of the amyloid abeta-(1-42) peptide of Alzheimer's disease.
  J Biol Chem, 277, 40173-40176.  
11912198 M.Palmblad, A.Westlind-Danielsson, and J.Bergquist (2002).
Oxidation of methionine 35 attenuates formation of amyloid beta -peptide 1-40 oligomers.
  J Biol Chem, 277, 19506-19510.  
12437582 Z.X.Yao, R.C.Brown, G.Teper, J.Greeson, and V.Papadopoulos (2002).
22R-Hydroxycholesterol protects neuronal cells from beta-amyloid-induced cytotoxicity by binding to beta-amyloid peptide.
  J Neurochem, 83, 1110-1119.  
11722581 R.Riek, P.Güntert, H.Döbeli, B.Wipf, and K.Wüthrich (2001).
NMR studies in aqueous solution fail to identify significant conformational differences between the monomeric forms of two Alzheimer peptides with widely different plaque-competence, A beta(1-40)(ox) and A beta(1-42)(ox).
  Eur J Biochem, 268, 5930-5936.  
10899428 L.C.Serpell (2000).
Alzheimer's amyloid fibrils: structure and assembly.
  Biochim Biophys Acta, 1502, 16-30.  
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.