PMID- 24070197
OWN - NLM
STAT- MEDLINE
DCOM- 20140508
LR  - 20131007
IS  - 1520-510X (Electronic)
IS  - 0020-1669 (Linking)
VI  - 52
IP  - 19
DP  - 2013 Oct 7
TI  - Zinc(II) interactions with brain-derived neurotrophic factor N-terminal peptide 
      fragments: inorganic features and biological perspectives.
PG  - 11075-83
LID - 10.1021/ic401318t [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal 
      differentiation, growth, and survival; it is involved in memory formation and 
      higher cognitive functions. The N-terminal domain of BDNF is crucial for the 
      binding selectivity and activation of its specific TrkB receptor. Zn(2+) ion 
      binding may influence BDNF activity. Zn(2+) complexes with the peptide fragment 
      BDNF(1-12) encompassing the sequence 1-12 of the N-terminal domain of BDNF were 
      studied by means of potentiometry, electrospray mass spectrometry, NMR, and 
      density functional theory (DFT) approaches. The predominant Zn(2+) complex 
      species, at physiological pH, is [ZnL] in which the metal ion is bound to an 
      amino, an imidazole, and two water molecules (NH2, N(Im), and 2O(water)) in a 
      tetrahedral environment. DFT-based geometry optimization of the zinc coordination 
      environment showed a hydrogen bond between the carboxylate and a water molecule 
      bound to zinc in [ZnL]. The coordination features of the acetylated form 
      [AcBDNF(1-12)] and of a single mutated peptide [BDNF(1-12)D3N] were also 
      characterized, highlighting the role of the imidazole side chain as the first 
      anchoring site and ruling out the direct involvement of the aspartate residue in 
      the metal binding. Zn(2+) addition to the cell culture medium induces an increase 
      in the proliferative activity of the BDNF(1-12) peptide and of the whole protein 
      on the SHSY5Y neuroblastoma cell line. The effect of Zn(2+) is opposite to that 
      previously observed for Cu(2+) addition, which determines a decrease in the 
      proliferative activity for both peptide and protein, suggesting that these metals 
      might discriminate and modulate differently the activity of BDNF.
FAU - Travaglia, Alessio
AU  - Travaglia A
AD  - Center for Neural Science, New York University , 4 Washington Place, New York, 
      New York 10003, United States.
FAU - La Mendola, Diego
AU  - La Mendola D
FAU - Magri, Antonio
AU  - Magri A
FAU - Pietropaolo, Adriana
AU  - Pietropaolo A
FAU - Nicoletti, Vincenzo G
AU  - Nicoletti VG
FAU - Grasso, Giuseppe
AU  - Grasso G
FAU - Malgieri, Gaetano
AU  - Malgieri G
FAU - Fattorusso, Roberto
AU  - Fattorusso R
FAU - Isernia, Carla
AU  - Isernia C
FAU - Rizzarelli, Enrico
AU  - Rizzarelli E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130926
PL  - United States
TA  - Inorg Chem
JT  - Inorganic chemistry
JID - 0366543
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Coordination Complexes)
RN  - 0 (Peptide Fragments)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/*chemistry/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Coordination Complexes/chemistry
MH  - Drug Stability
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Molecular Structure
MH  - Peptide Fragments/*chemistry/metabolism
MH  - *Quantum Theory
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Zinc/*chemistry/pharmacology
EDAT- 2013/09/28 06:00
MHDA- 2014/05/09 06:00
CRDT- 2013/09/28 06:00
PHST- 2013/09/28 06:00 [entrez]
PHST- 2013/09/28 06:00 [pubmed]
PHST- 2014/05/09 06:00 [medline]
AID - 10.1021/ic401318t [doi]
PST - ppublish
SO  - Inorg Chem. 2013 Oct 7;52(19):11075-83. doi: 10.1021/ic401318t. Epub 2013 Sep 26.