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PDBsum entry 1ze9

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protein metals links
Metal binding protein PDB id
1ze9
Jmol
Contents
Protein chain
18 a.a.
Metals
_ZN
PDB id:
1ze9
Name: Metal binding protein
Title: Zinc-binding domain of alzheimer's disease amyloid beta-pept complexed with a zinc (ii) cation
Structure: 16-mer from alzheimer's disease amyloid protein. Chain: a. Synonym: alzheimer's disease amyloid a4 protein, amyloid be protein. Engineered: yes
Source: Synthetic: yes. Other_details: this sequence occurs naturally in humans.
NMR struc: 20 models
Authors: S.Zirah,S.A.Kozin,A.K.Mazur,A.Blond,M.Cheminant,I.Segalas-Mi P.Debey,S.Rebuffat
Key ref:
S.Zirah et al. (2006). Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging. J Biol Chem, 281, 2151-2161. PubMed id: 16301322 DOI: 10.1074/jbc.M504454200
Date:
18-Apr-05     Release date:   03-May-05    
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.
17 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1074/jbc.M504454200 J Biol Chem 281:2151-2161 (2006)
PubMed id: 16301322  
 
 
Structural changes of region 1-16 of the Alzheimer disease amyloid beta-peptide upon zinc binding and in vitro aging.
S.Zirah, S.A.Kozin, A.K.Mazur, A.Blond, M.Cheminant, I.Ségalas-Milazzo, P.Debey, S.Rebuffat.
 
  ABSTRACT  
 
Amyloid deposits within the cerebral tissue constitute a characteristic lesion associated with Alzheimer disease. They mainly consist of the amyloid peptide Abeta and display an abnormal content in Zn(2+) ions, together with many truncated, isomerized, and racemized forms of Abeta. The region 1-16 of Abeta can be considered the minimal zinc-binding domain and contains two aspartates subject to protein aging. The influence of zinc binding and protein aging related modifications on the conformation of this region of Abeta is of importance given the potentiality of this domain to constitute a therapeutic target, especially for immunization approaches. In this study, we determined from NMR data the solution structure of the Abeta-(1-16)-Zn(2+) complex in aqueous solution at pH 6.5. The residues His(6), His(13), and His(14) and the Glu(11) carboxylate were identified as ligands that tetrahedrally coordinate the Zn(II) cation. In vitro aging experiments on Abeta-(1-16) led to the formation of truncated and isomerized species. The major isomer generated, Abeta-(1-16)-l-iso-Asp(7), displayed a local conformational change in the His(6)-Ser(8) region but kept a zinc binding propensity via a coordination mode involving l-iso-Asp(7). These results are discussed here with regard to Abeta fibrillogenesis and the potentiality of the region 1-16 of Abeta to be used as a therapeutic target.
 
  Selected figure(s)  
 
Figure 3.
Main sequential and medium range NOEs observed for Aβ-(1-16) at pH 6.5 in the absence (black) and in the presence (gray) of Zn^2+. The thickness of the bars illustrates the relative cross-peak intensities.
Figure 5.
Structure of the Aβ-(1-16)-Zn^2+ complex at pH 6.5 calculated with the ICMD protocol. A and B, views showing the location of the zinc ion, which is coordinated through the imidazole nitrogens of the three histidine, His^6, His^13, and His^14, side chains and the carboxylate of the Glu^11 side chain. C and D, corresponding electrostatic molecular surface of the complex; C, view is rotated 180° about the x axis relative to the A view. Blue and red correspond to negatively and positively charged areas, respectively.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 2151-2161) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20354739 N.Sawada, N.Nagahara, F.Arisaka, K.Mitsuoka, and M.Minami (2011).
Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation.
  Amino Acids, 41, 173-180.  
21350790 S.A.Kozin, Y.V.Mezentsev, A.A.Kulikova, M.I.Indeykina, A.V.Golovin, A.S.Ivanov, P.O.Tsvetkov, and A.A.Makarov (2011).
Zinc-induced dimerization of the amyloid-β metal-binding domain 1-16 is mediated by residues 11-14.
  Mol Biosyst, 7, 1053-1055.  
21359283 V.Tõugu, A.Tiiman, and P.Palumaa (2011).
Interactions of Zn(ii) and Cu(ii) ions with Alzheimer's amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity.
  Metallomics, 3, 250-261.  
19923222 G.S.Basi, H.Feinberg, F.Oshidari, J.Anderson, R.Barbour, J.Baker, T.A.Comery, L.Diep, D.Gill, K.Johnson-Wood, A.Goel, K.Grantcharova, M.Lee, J.Li, A.Partridge, I.Griswold-Prenner, N.Piot, D.Walker, A.Widom, M.N.Pangalos, P.Seubert, J.S.Jacobsen, D.Schenk, and W.I.Weis (2010).
Structural correlates of antibodies associated with acute reversal of amyloid beta-related behavioral deficits in a mouse model of Alzheimer disease.
  J Biol Chem, 285, 3417-3427.
PDB codes: 3ifl 3ifn 3ifo 3ifp
20556483 J.Y.Lee, E.Cho, T.Y.Kim, D.K.Kim, R.D.Palmiter, I.Volitakis, J.S.Kim, A.I.Bush, and J.Y.Koh (2010).
Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain.
  Biometals, 23, 1085-1095.  
20104355 M.A.Zoroddu, S.Medici, M.Peana, and R.Anedda (2010).
NMR studies of zinc binding in a multi-histidinic peptide fragment.
  Dalton Trans, 39, 1282-1294.  
21081056 P.O.Tsvetkov, A.A.Kulikova, A.V.Golovin, Y.V.Tkachev, A.I.Archakov, S.A.Kozin, and A.A.Makarov (2010).
Minimal Zn(2+) binding site of amyloid-β.
  Biophys J, 99, L84-L86.  
21209855 S.C.Drew, C.L.Masters, and K.J.Barnham (2010).
Alzheimer's Aβ peptides with disease-associated N-terminal modifications: influence of isomerisation, truncation and mutation on Cu2+ coordination.
  PLoS One, 5, e15875.  
20402519 Y.Miller, B.Ma, and R.Nussinov (2010).
Polymorphism in Alzheimer Abeta amyloid organization reflects conformational selection in a rugged energy landscape.
  Chem Rev, 110, 4820-4838.  
20448202 Y.Miller, B.Ma, and R.Nussinov (2010).
Zinc ions promote Alzheimer Abeta aggregation via population shift of polymorphic states.
  Proc Natl Acad Sci U S A, 107, 9490-9495.  
19549187 A.Olofsson, M.Lindhagen-Persson, M.Vestling, A.E.Sauer-Eriksson, and A.Ohman (2009).
Quenched hydrogen/deuterium exchange NMR characterization of amyloid-beta peptide aggregates formed in the presence of Cu2+ or Zn2+.
  FEBS J, 276, 4051-4060.  
19083027 C.Talmard, R.Leuma Yona, and P.Faller (2009).
Mechanism of zinc(II)-promoted amyloid formation: zinc(II) binding facilitates the transition from the partially alpha-helical conformer to aggregates of amyloid beta protein(1-28).
  J Biol Inorg Chem, 14, 449-455.  
19322475 P.Faller, and C.Hureau (2009).
Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-beta peptide.
  Dalton Trans, (), 1080-1094.  
19619132 V.Tõugu, A.Karafin, K.Zovo, R.S.Chung, C.Howells, A.K.West, and P.Palumaa (2009).
Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators.
  J Neurochem, 110, 1784-1795.  
19040415 Y.Biran, C.L.Masters, K.J.Barnham, A.I.Bush, and P.A.Adlard (2009).
Pharmacotherapeutic targets in Alzheimer's disease.
  J Cell Mol Med, 13, 61-86.  
18489171 I.H.Chou, M.Benford, H.T.Beier, G.L.Coté, M.Wang, N.Jing, J.Kameoka, and T.A.Good (2008).
Nanofluidic biosensing for beta-amyloid detection using surface enhanced Raman spectroscopy.
  Nano Lett, 8, 1729-1735.  
18085519 I.Y.Toropygin, E.V.Kugaevskaya, O.A.Mirgorodskaya, Y.E.Elisseeva, Y.P.Kozmin, I.A.Popov, E.N.Nikolaev, A.A.Makarov, and S.A.Kozin (2008).
The N-domain of angiotensin-converting enzyme specifically hydrolyzes the Arg-5-His-6 bond of Alzheimer's Abeta-(1-16) peptide and its isoAsp-7 analogue with different efficiency as evidenced by quantitative matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
  Rapid Commun Mass Spectrom, 22, 231-239.  
18506864 P.O.Tsvetkov, I.A.Popov, E.N.Nikolaev, A.I.Archakov, A.A.Makarov, and S.A.Kozin (2008).
Isomerization of the Asp7 residue results in zinc-induced oligomerization of Alzheimer's disease amyloid beta(1-16) peptide.
  Chembiochem, 9, 1564-1567.  
18594731 V.A.Streltsov, and J.N.Varghese (2008).
Substrate mediated reduction of copper-amyloid-beta complex in Alzheimer's disease.
  Chem Commun (Camb), (), 3169-3171.  
18599641 V.A.Streltsov, S.J.Titmuss, V.C.Epa, K.J.Barnham, C.L.Masters, and J.N.Varghese (2008).
The structure of the amyloid-beta peptide high-affinity copper II binding site in Alzheimer disease.
  Biophys J, 95, 3447-3456.  
18004559 V.Streltsov (2008).
X-ray absorption and diffraction studies of the metal binding sites in amyloid beta-peptide.
  Eur Biophys J, 37, 257-263.  
17517595 A.Muhs, D.T.Hickman, M.Pihlgren, N.Chuard, V.Giriens, C.Meerschman, I.van der Auwera, F.van Leuven, M.Sugawara, M.C.Weingertner, B.Bechinger, R.Greferath, N.Kolonko, L.Nagel-Steger, D.Riesner, R.O.Brady, A.Pfeifer, and C.Nicolau (2007).
Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice.
  Proc Natl Acad Sci U S A, 104, 9810-9815.  
17828365 C.Kállay, K.Osz, A.Dávid, Z.Valastyán, G.Malandrinos, N.Hadjiliadis, and I.Sóvágó (2007).
Zinc(II) binding ability of tri-, tetra- and penta-peptides containing two or three histidyl residues.
  Dalton Trans, (), 4040-4047.  
17195250 C.Talmard, L.Guilloreau, Y.Coppel, H.Mazarguil, and P.Faller (2007).
Amyloid-beta peptide forms monomeric complexes with Cu(II) and Zn(II) prior to aggregation.
  Chembiochem, 8, 163-165.  
17222176 J.Danielsson, R.Pierattelli, L.Banci, and A.Gräslund (2007).
High-resolution NMR studies of the zinc-binding site of the Alzheimer's amyloid beta-peptide.
  FEBS J, 274, 46-59.  
17107881 J.Dong, K.Lu, A.Lakdawala, A.K.Mehta, and D.G.Lynn (2006).
Controlling amyloid growth in multiple dimensions.
  Amyloid, 13, 206-215.  
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.  
16820299 K.J.Barnham, R.Cappai, K.Beyreuther, C.L.Masters, and A.F.Hill (2006).
Delineating common molecular mechanisms in Alzheimer's and prion diseases.
  Trends Biochem Sci, 31, 465-472.  
16924555 L.Guilloreau, L.Damian, Y.Coppel, H.Mazarguil, M.Winterhalter, and P.Faller (2006).
Structural and thermodynamical properties of CuII amyloid-beta16/28 complexes associated with Alzheimer's disease.
  J Biol Inorg Chem, 11, 1024-1038.  
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.